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Immunosuppressive
Terms modified by Immunosuppressive Selected AbstractsImmunocompetence of bivalve hemocytes as evaluated by a miniaturized phagocytosis assayENVIRONMENTAL TOXICOLOGY, Issue 3 2002C. Blaise Abstract Immune function in bivalves can be adversely affected by long-term exposure to environmental contaminants. Investigating alterations in immunity can therefore yield relevant information about the relationship between exposure to environmental contaminants and susceptibility to infectious diseases. We have developed a rapid, cost-effective, and miniaturized immunocompetence assay to evaluate the phagocytic activity, viability, and concentration of hemocytes in freshwater and marine bivalves. Preliminary experiments were performed to optimize various aspects of the assay including 1) the time required for adherence of hemocytes to polystyrene microplate wells, 2) the time required for internalization of fluorescent bacteria, 3) the ratio of hemocytes to fluorescent bacteria in relation to phagocytosis, 4) hemolymph plasma requirements, and 5) the elimination of fluorescence from (noninternalized) bacteria adhering to the external surface of hemocytes. The results of these experiments showed the optimal adherence time for hemocytes in microplate wells to be 1 h, that phagocytosis required at least 2 h of contact with fluorescently labeled E. coli cells, that the number of fluorescent E. coli cells had a positive effect on phagocytic activity, that at least 2.5 million cells/mL were required to measure a significant intake, and that a linear increase in uptake of bacteria (R = 0.91; p < 0.01) could be obtained with concentrations of up to 1.3 × 106 hemocytes/mL. Afterward, the assay was used in two field studies to identify sites having the potential to affect the immunocompetence of bivalves. The first study was conducted on Mya arenaria clams collected at selected contaminated sites in the Saguenay River (Quebec, Canada), and the second examined Elliptio complanata freshwater bivalves that had been exposed to a municipal effluent plume in the St. Lawrence River (Quebec, Canada). In the Saguenay River field study a significant increase in phagocytosis was observed at sites closest to polluted areas. Phagocytotic activity varied over time and was highest during the warmest months (June, July, and August), closely paralleling the spawning period of Mya arenaria clams. In contrast, a drop in phagocytic activity was observed in Elliptio complanata mussels exposed to surface water 4 km downstream of a major municipal effluent plume, with a concomitant increase in the number of hemocytes in the hemolymph. It appears that both immunosuppressive and immunostimulative effects are likely to occur in the field and that responses will be influenced by the type and intensity of contaminants at play. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 160,169, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10047 [source] Determinants of within- and among-clutch variation in levels of maternal hormones in Black-Headed Gull eggsFUNCTIONAL ECOLOGY, Issue 3 2002Groothuis T. G. Summary 1.,Females of egg-laying vertebrates may adjust the development of their offspring to prevailing environmental conditions by regulating the deposition of hormones into their eggs. Within- and amng-clutch variation in levels of steroid hormones were studied in the egg yolks of the Black-Headed Gull (Larus ridibundus, Linnaeus) in relation to environmental conditions at the nest site. This species breeds in colonies of different densities and in different habitats, and the chicks hatch asynchronously. 2.,Egg yolks contained very high levels of androstenedione, substantial levels of testosterone and moderate levels of 5,-dihydrotestosterone. Oestrogen (17,-oestradiol) was not detected. 3.,Androgen levels increased strongly with laying order, irrespective of egg or yolk mass. This may compensate for the disadvantages of the later hatching chicks. These results have implications for adaptive hypotheses that were proposed for asynchronous incubation. 4.,Eggs of lighter clutches contained more androgens, perhaps to compensate for a lower nutritional quality of these eggs. 5.,Birds breeding in the periphery of a colony, being relatively more aggressive and having relatively large territories, laid eggs that contained more androgens than those of birds breeding in the centre. These high yolk androgen levels may facilitate growth and motor development of the chicks, which may be especially important for chicks developing at the periphery of a colony. Reduced levels may be adaptive for birds breeding in the centre, where risk of infectious diseases is high, since steroids may be immunosuppressive. 6.,Corrected for nest distance, clutches of birds in high vegetation, where predation risk is less severe and therefore competition for nest sites perhaps high, contained relatively high levels of androgens. It is suggested that the level of yolk androgens reflects the hormonal condition of the female, that in turn is influenced by her characteristics such as her age and aggressiveness, and the level of social stimulation. [source] Leflunomide protects from T-cell,mediated liver injury in mice through inhibition of nuclear factor ,BHEPATOLOGY, Issue 5 2004Motoaki Imose Leflunomide is a novel immunosuppressive and anti-inflammatory agent for the treatment of autoimmune disease. The aim of this study was to investigate whether leflunomide protects from liver injury induced by concanavalin A (Con A), a T-cell,dependent model of liver damage. BALB/c mice were injected with 25 mg/kg Con A in the presence or absence of 30 mg/kg leflunomide. Liver injury was assessed biochemically and histologically. Levels of circulating cytokines and expressions of cytokine messenger RNA (mRNA) in the liver and the spleen were determined. Treatment with leflunomide markedly reduced serum transaminase activities and the numbers of dead liver cells. Leflunomide significantly inhibited increases in plasma tumor necrosis factor alpha (TNF-,) and interleukin 2 concentrations, and also reduced TNF-, mRNA expression in the liver after administration of Con A. These findings were supported by the results in which leflunomide administration decreased the number of T lymphocytes infiltrating the liver as well as inhibiting their production of TNF-,. Activation of nuclear factor ,B (NF-,B), which regulates TNF-, production, was inhibited in the liver of mice treated with leflunomide, resulting in a reduction of TNF-, production from lymphocytes infiltrating the liver. In conclusion, leflunomide is capable of regulating T-cell,mediated liver injury in vivo and that this event may depend on the decrease of TNF-, production in the liver through inhibition of NF-,B activation caused by leflunomide. (HEPATOLOGY 2004.) [source] Lymphoma risk in inflammatory bowel disease: Is it the disease or its treatment?INFLAMMATORY BOWEL DISEASES, Issue 10 2007Jennifer L. Jones MD Abstract With the increasingly widespread use of immunosuppressive and biologic agents for the treatment of Crohn's disease and ulcerative colitis come concerns about potential long-term consequences of such therapies. Disentangling the potential confounding effects of the underlying disease, its extent, severity, duration, and behavior, and concomitant medical therapy has proven to be exceedingly difficult. Unlike the case in rheumatoid arthritis, the overwhelming preponderance of population-based evidence suggests that a diagnosis of inflammatory bowel disease (IBD) is not associated with an increased relative risk of lymphoma. However, well-designed studies that evaluate the potential modifying effect of IBD severity have yet to be performed. Although the results from hospital- and population-based studies have conflicted, the results of a recent meta-analysis suggest that patients receiving purine analogs for the treatment of IBD have a lymphoma risk ,4-fold higher than expected. Analyses of lymphoma risk in patients receiving biologic agents directed against tumor necrosis factor-alpha are confounded by concomitant use of immunosuppressive agents in most of these patients. Nevertheless, there may be a small but real risk of lymphoma associated with these therapies. Although the relative risk of lymphoma may be elevated in association with some of the medical therapies used in the treatment of IBD, this absolute risk is low. Weighing the potential risk of lymphoma associated with select medical therapies against the risk of undertreating IBD will help physicians and patients to make more informed decisions pertaining to the medical management of IBD. (Inflamm Bowel Dis 2007) [source] Efficacy and tolerance of infliximab in children and adolescents with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 6 2004Dr. Thierry Lamireau Abstract Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3,17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8,7.3) of infliximab during a median time period of 4 months (1,17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey,Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment. [source] Could immunosuppressive drugs reduce recurrence rate after second resection for crohn disease?INFLAMMATORY BOWEL DISEASES, Issue 5 2004Arnaud Alves MD Abstract Background: The aim of this study was to assess the possible benefit of postoperative immunosuppressive drugs administration (ie, azathioprine, 6-mercaptopurine, or methotrexate) on long-term surgical recurrence rate after second anastomotic ileocolonic resection. Methods: From 1984 to 2000, 26 patients with CD underwent second resection for ileocolonic anastomotic recurrence. There were 14 women and 12 men (mean age ± SD: 34 ± 9 years). Two groups of patients were compared according to the postoperative treatment: immunosuppressive (IS) drugs group was composed of 14 patients, and control group was composed of 12 patients receiving either salicylates (n = 5) or no treatment (n = 7). Results: Clinical recurrence rate at 3 years was significantly lower in the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05). Although not significant, after a mean follow-up of 80 ± 46 months (extr. 17,178 months) after the second resection, clinical recurrence rate at follow-up was also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean delay of recurrence was similar in both groups (27 ± 13 months vs 28 ± 21; NS). A third intestinal resection was performed less frequently in the IS group than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). Conclusions: In patients treated with IS drugs, the rate of postoperative recurrence after second ileocolonic CD resection is lower than in untreated patients. Our results suggest that IS drugs should be evaluated prospectively for prevention of second postoperative CD recurrence. [source] Alpha-1-antitrypsin deficiency associated with panniculitis treated with plasma exchange therapyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004Priscila De Oliveira MD Background, Alpha-1-antitrypsin is the principal serum protease inhibitor. In addition to the well-recognized association with early-onset emphysema and cirrhosis, alpha-1-antitrypsin deficiency may be associated with panniculitis. The treatment of this type of panniculitis presents a significant challenge. Previous attempts using immunosuppressive, anti-inflammatory, and cytotoxic drugs have shown variable results. Aim, To report a case of alpha-1-antitrypsin deficiency-associated panniculitis treated with plasma exchange therapy. Methods, A 23-year-old patient developed painful red nodules on her thighs and buttocks with spontaneous ulceration and discharge of oily fluid. A skin biopsy specimen showed septal and lobular panniculitis. The serum alpha-1-antitrypsin level was 22 mg/dL. She was treated with plasma exchange therapy. Results, Treatment of this patient with plasma exchange therapy led to the control of the cutaneous lesions. Conclusions, Plasma exchange therapy represents an alternative treatment which restores serum and tissue alpha-1-antitrypsin levels. This method is proposed because of its clinical benefits and greater availability. [source] Role of splenectomy in patients with refractory or relapsed thrombotic thrombocytopenic purpuraJOURNAL OF CLINICAL APHERESIS, Issue 2 2003Nicole A. Aqui Abstract Thrombotic thrombocytopenic purpura (TTP) was once uniformly fatal. Therapeutic plasma exchange in combination with immunosuppressive and anti-platelet agents, however, have resulted in improved survival rates of greater than 80% for patients with TTP. In spite of aggressive plasma exchange and adjuvant therapy, a number of TTP patients are refractory to treatment. In addition, up to 40% of TTP patients who initially respond to therapy eventually relapse. Alternative therapies such as splenectomy have been used with varying degrees of success in refractory and relapsing TTP patients. The usefulness of splenectomy in preventing relapse of TTP or treating those patients who are refractory to plasma exchange remains controversial. We present a single institution's experience with 14 patients who underwent splenectomy for refractory (six patients) or relapsed (eight patients) TTP since 1984. In both patient groups, splenectomy induced stable long-term remissions. Six of six (100%) patients who were refractory to plasma exchange, survived to be discharged from the hospital, apparently free of disease. Four of eight patients (50%) who had a splenectomy for relapsing TTP went into a complete remission and had no further relapses of their disease. Moreover, in relapsing patients who failed to experience long-term remission, the relapse rate after splenectomy was 0.3 events per patient year compared to 1.0 events per patient year prior to splenectomy. We conclude that splenectomy is a reasonable treatment option for TTP patients refractory to standard plasma exchange therapy or who have experienced multiple and/or complicated relapses. We believe this is the first series that demonstrates efficacy of splenectomy in plasma exchange-refractory TTP. J. Clin. Apheresis 18:51,54, 2003. © 2003 Wiley-Liss, Inc. [source] The novel application of an immunological technique reveals the immunosuppressive effect of phytoestrogens in Betta splendensJOURNAL OF FISH BIOLOGY, Issue A 2006D. R. Ardia The novel application of a standard technique to assess cell-mediated immune response to phytohaemagglutinin (PHA) injected in the caudal peduncle in a small fish (<2 g) to test the immunosuppressive effect of three phytoestrogens: genistein, equol and ,-sitosterol is described. Individual Betta splendens exposed to these oestrogenic chemicals produced weaker inflammatory responses to PHA than did control individuals, suggesting that phytoestrogens are immunosuppressive. This technique should enable immune function in fish species, too small to provide sufficient blood for conventional immunological measures, to be assessed. [source] Synthesis of isomeric 2,3,5-trisubstituted perhydropyrrolo[3,4-d]-isoxazole-4,6-diones via 1,3-dipolar cycloaddition reactionsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2010Hamdi Özkan A series of isoxazolidine derivates (isomeric 2,3,5-trisubstitutedperhydropyrrolo[3,4-d]isoxazole-4,6-diones) used as anti-inflammatory, immunosuppressive, antibacterial agent, and inhibitor for some enzymes were synthesized. These compounds were prepared by 1,3-dipolar cycloaddition of N -methyl maleimide and N -phenyl maleimide with nitrones. Diastereomeric products obtained in this reaction were separated by column chromatography and recrystallized. All compounds synthesized were characterized by elemental analysis and spectroscopic methods (1H NMR, 13C NMR, and FTIR). J. Heterocyclic Chem., (2010). [source] Immunomodulation by mesenchymal stem cells and clinical experienceJOURNAL OF INTERNAL MEDICINE, Issue 5 2007K. Le Blanc Abstract Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders. [source] Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study,JOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Olga Garkavenko Abstract Shortage of human donor organs for transplantation has prompted usage of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonoses remain. Despite careful monitoring of designated pathogen free pigs there is still a risk that their tissues may carry infectious agents. Thus xenotransplantation requires extensive pre-clinical study on safety of the graft especially for those viruses that are either potentially oncogenic and/or immunosuppressive, or can establish persistent infection. A prospective pig-to-primate islet xenotransplantation study was performed which includes monitoring for potentially xenotic viruses namely porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), porcine lymphotropic herpesvirus (PLHV), and porcine circovirus (PCV) using both molecular diagnostic,PCR and RT-PCR and serology methods. There was no evidence of pig virus transmission into primate recipients. This preclinical study underlines the information concerning viral safety of islet cell xenograft in pig-to-primate xenotransplantation. J. Med. Virol. 80:2046,2052, 2008. © 2008 Wiley-Liss, Inc. [source] Cyclopeptides of Linum usitatissimumJOURNAL OF PEPTIDE SCIENCE, Issue 9 2006Boles, aw Picur Abstract Cyclolinopeptide A (CLA), a cyclic nonapeptide from linseed, possesses strong immunosuppressive and antimalarial activity along with the ability to inhibit cholate uptake into hepatocytes. The structure of the peptide was studied extensively in solution as well as in the solid state. It is postulated that both the Pro,Pro cis -amide bond and an ,edge-to-face' interaction between the aromatic rings of two adjacent Phe residues are important for biological activity. Structure,activity relationship studies of many linear and cyclic analogues of CLA suggest that the Pro-Xxx-Phe sequence and the flexibility of the peptide are important for the immunosuppressive activity. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Comparison of suppressive potency between prednisolone and prednisolone sodium succinate against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001Kentaro Sugiyama Clinically, both prednisolone and prednisolone sodium succinate are widely used as immunosuppressive agents for the treatment of various allergic disorders. However, whether prednisolone sodium succinate itself has immunosuppressive or anti-inflammatory effects is unclear, and prednisolone sodium succinate may exhibit its efficacy only after hydrolytic conversion to prednisolone in-vivo. If this is the case, the impairment of prednisolone sodium succinate conversion to prednisolone in some clinical conditions may attenuate the efficacy of prednisolone sodium succinate. We therefore compared the pharmacological efficacy of prednisolone with that of prednisolone sodium succinate in-vitro using human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from 5 healthy subjects and 1 patient with pneumonia. The cells were incubated in the presence of concanavalin A and the cell growth was estimated by 3-(4,5-dimethyl thiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Both prednisolone and prednisolone sodium succinate dose-dependently suppressed PBMC blastogenesis. Mean (s.d.) prednisolone and prednisolone sodium succinate IC50 (concentration of drug that gave 50% inhibition of cell growth) values were 580.0 (1037.9) and 3237.1 (4627.3) nm, respectively. The ratio of prednisolone IC50/prednisolone sodium succinate IC50 ranged from 0.005 to 0.230. Thus, prednisolone sodium succinate potency was markedly lower than that of prednisolone. After incubation of PBMCs with 100 ,m prednisolone sodium succinate, 22.7,42.9 ,m prednisolone was liberated into the culture medium, as determined by HPLC. The ratio of prednisolone liberation from prednisolone sodium succinate was not affected by the presence of fetal bovine serum or PBMC, or both, in the culture medium. These results suggested that the PBMC-suppressive effects of prednisolone sodium succinate might be due, at least partially, to prednisolone liberated from prednisolone sodium succinate into the culture medium. Prednisolone sodium succinate can be converted to prednisolone in the absence of serum or PBMCs, but the ratio of this conversion was very slow (t£frac12; > 4 days). Therefore, impairment of the enzymatic conversion of prednisolone sodium succinate to prednisolone in some pathological conditions such as liver diseases may result in attenuation of the clinical efficacy of prednisolone sodium succinate. [source] Review article: the gastrointestinal complications of myositisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010E. C. EBERT Aliment Pharmacol Ther,31, 359,365 Summary Background, The inflammatory myopathies are a group of acquired diseases characterized by a proximal myopathy caused by an inflammatory infiltrate of the skeletal muscle. The three major diseases are dermatomyositis, polymyositis and inclusion body myositis. Aims, To review the gastrointestinal manifestations of myositis. Methods, Over 110 articles in the English literature were reviewed. Results, Dysphagia to solids and liquids occurs in patients with myositis. The pharyngo-oesophageal muscle tone is lost and therefore patients develop nasal speech, hoarseness, nasal regurgitation and aspiration pneumonia. There is tongue weakness, flaccid vocal cords, poor palatal motion and pooling of secretions in the distended hypopharynx. Proximal oesophageal skeletal muscle dysfunction is demonstrated by manometry with low amplitude/absent pharyngeal contractions and decreased upper oesophageal sphincter pressures. Patients exhibit markedly elevated creatine kinase and lactate dehydrogenase levels consistent with muscle injury. Myositis can be associated with inflammatory bowel disease, coeliac disease and interferon treatment of hepatitis C. Corticosteroids and other immunosuppressive drugs comprise the mainstay of treatment. Inclusion body myositis responds poorly to these agents and therefore a myotomy is usually indicated. Conclusion, Myositis mainly involves the skeletal muscles in the upper oesophagus with dysphagia, along with proximal muscle weakness. [source] Infliximab treatment for symptomatic Crohn's disease stricturesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009A.-L. PELLETIER Summary Background, Some reports have suggested that infliximab may induce obstructive symptoms and, although there is no firm evidence, it is usually contra-indicated in-patients with Crohn's disease (CD) and strictures. Aims, To evaluate the effect of infliximab on symptomatic strictures of the small intestine in CD and to identify predictive factors of clinical response. Methods, This retrospective study included symptomatic patients treated with infliximab after conventional treatment had failed. The short-term (week 8) and long-term results were classified according to predefined criteria as complete, partial response, or failure. Results, Before infliximab, 18 patients had complete obstruction or intermittent chronic abdominal pain. Fourteen patients were treated by corticosteroids and 13 received immunosuppressive drugs. At week 8, complete, partial response and failure were observed in 10, 7 and 1 patients, respectively. Fourteen patients continued maintenance infliximab treatment after week 8. During the most recent evaluation (median follow-up: 18 months), 8 patients were on maintenance infliximab treatment; only eight were still on prednisone; there were five complete responses, 10 partial responses and three failures. Initiating prednisone or increasing its dosage was the only factor associated with a short-term complete response. Conclusions, Infliximab may be effective in patients with symptomatic strictures from CD, and should be tested before considering surgery. [source] Review article: steroid resistance in inflammatory bowel disease , mechanisms and therapeutic strategiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007T. J. CREED Summary Background Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options. Methods We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids. Results Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40,60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin-2. Basiliximab, a biological agent that interrupts interleukin-2 signalling, has shown significant benefit in early clinical studies. Conclusions Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging. [source] Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney diseaseNEPHROLOGY, Issue 3 2010PAOLO FERRARI ABSTRACT Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin-6 (IL-6) and improved iron mobilization. Background: CKD patients may have elevated IL-6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL-6 expression. Methods: We studied 14 patients with stages 4,5 CKD (glomerular filtration rate <30mL/min per 1.73 m2) due to non-inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin-stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run-in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run-in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL-6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL-6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL-6 and improves haemoglobin in non-inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin. [source] Mesenchymal stem cells: Immunobiology and therapeutic potential in kidney disease (Review Article)NEPHROLOGY, Issue 1 2007STEVEN J MCTAGGART SUMMARY: Mesenchymal stem cells (MSC) are non-haematopoietic cells that are prevalent in the adult bone marrow but can also be isolated from a variety of other postnatal tissues. MSC are non-immunogenic and are immunosuppressive, with the ability to inhibit maturation of dendritic cells and suppress the function of naïve and memory T cells, B cells and NK cells. In addition to their immunomodulatory properties, MSC are capable of differentiating into various tissues of mesenchymal and non-mesenchymal origin and migrating to sites of tissue injury and inflammation to participate in tissue repair. A number of studies in animal models of cardiac injury, stroke and ischaemic renal injury have demonstrated the clinical potential of MSC in tissue regeneration and repair. MSC are currently being evaluated in various preclinical and clinical studies in humans and offer significant potential as a novel cellular therapy for tissue regeneration and immunological conditions. The present review focuses on the unique immunomodulatory and regenerative properties of MSC and their potential role in the treatment of kidney disease. [source] Number III Mucous membrane pemphigoidORAL DISEASES, Issue 4 2005J Bagan Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory,especially immunosuppressive,therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Adverse drug reactions in patients in an Iranian department of internal medicine,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2009Sara Pourseyed MD Abstract Purpose Adverse drug reactions (ADRs) are a major cause of hospital admission and inpatient morbidity. The department of internal medicine is not an exception to this issue. This study was performed to determine the nature and frequency of ADRs in an internal medicine ward in Iran. Methods This survey was a prospective observational study based on admissions of 400 patients to the internal medicine ward over a 15-week period. Patients were intensively followed in order to assess any ADR as a cause of admission or occurring during hospitalization. Any suspicious ADR was confirmed by a pharmacist/pharmacologist. Results There were 47 patients of 400 patients (11.75%) that experienced at least one ADR. ADR leading to the admission was seen in seven cases (1.75%) and in 40 (10%) it occurred during hospitalization. ADRs were identified as preventable reactions in 50% of cases and as predictable in 94.3%. The severity of 18.6% of the ADRs was identified as mild, 62.9% as moderate, 14.3% as severe and 4.3% as lethal. Gastrointestinal system disorders (44.3%) represented the most frequent ADRs. The therapeutic groups that most commonly associated with suspected ADRs were antineoplastic, immunosuppressive and medicines used in palliative care (54.8%). Conclusions ADRs are common among hospitalized patients in department of internal medicine and can be severe and even lethal. Since most ADRs occurred during hospitalization in studied patients and half of them were preventable, prevention strategies should be considered in hospitals. Also, our findings confirmed the role of hospital pharmacists in the reducing ADRs. Copyright © 2008 John Wiley & Sons, Ltd. [source] REVIEW ARTICLE: The Role of Placental Exosomes in ReproductionAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Lucia Mincheva-Nilsson Citation Mincheva-Nilsson L, Baranov V. The Role of Placental Exosomes in Reproduction. Am J Reprod Immunol 2010 Cell communication comprises cell,cell contact, soluble mediators and intercellular nanotubes. There is, however, another cell,cell communication by released membrane-bound microvesicles that convey cell,cell contact ,by proxy' transporting signals/packages of information from donor to recipient cells locally and/or at a distance. The nanosized exosomes comprise a specialized type of microvesicles generated within multivesicular bodies (MVB) and released upon MVB fusion with the plasma membrane. Exosomes are produced by a variety of immune, epithelial and tumor cells. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells. Recently, it was discovered that the syncytiotrophoblast constitutively and throughout the pregnancy secretes exosomes. The placenta-derived exosomes are immunosuppressive and carry proteins and RNA molecules that in a redundant way influence a number of mechanisms and promote the fetal allograft survival. In this review, we summarize the current knowledge on the nature of placenta-derived exosomes and discuss their role in pregnancy. [source] The ,Indirect' Effects of Cytomegalovirus InfectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009R. B. Freeman Cytomegalovirus (CMV) remains the most important infection in the immunocompromized host even in the era of effective therapy. CMV is usually acquired early in life and can be transmitted by contact with infected body fluids. In the immunocompetent population, primary infection is almost always of little clinical consequence. However, CMV infection in immunocompromized patients, especially those naive to CMV exposure, can cause tissue invasive disease, severe symptoms and/or death. However, beyond these direct effects, increasing in vitro evidence is accumulating that suggests CMV has many other effects on the host's immune response which may explain some of the detrimental consequences for the immunosuppressed patient, and may also be partially responsible for a variety of conditions in immunocompetent individuals. In its latent state, CMV employs several mechanisms to evade detection by the host's immune system. The virus also employs other methods to take advantage of activation of the immune system and replicate in sites of inflammation. This review focuses on the immunosuppressive and inflammatory mechanisms that have been attributed to CMV and will relate them to some of the clinical sequellae that have been associated with the indirect effects of CMV infection. [source] Treatment-dependent Loss of Polyfunctional CD8+ T-cell Responses in HIV-infected Kidney Transplant Recipients Is Associated with Herpesvirus ReactivationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009O. Gasser Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases. [source] CTLA-4Ig in Combination with Anti-CD40L Prolongs Xenograft Survival and Inhibits Anti-Gal Ab Production in GT-Ko MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2002Dengping Yin The generation of GT-Ko mice has provided unique opportunities to study allograft and xenograft rejection in the context of anti-,1,3-Gal antibody (anti-Gal Ab) responses. In this study we used the allotransplantation model of C3H hearts into galactosyltransferase-deficient (GT-Ko) mice and the xenotransplantation model of baby Lewis rat hearts into GT-Ko mice to investigate the ability of CTLA-4Ig in combination with anti-CD40L mAb to control graft rejection and anti-Gal Ab production. Murine CTLA-4Ig or anti-CD40L monotherapy prolonged allograft survival, and the combination of these reagents was most immunosuppressive. However short-term treatment with murine cytotoxic T lymphocyte associated antigen-4 (muCTLA-4Ig) and/or CD40 ligand (CD154) monoclonal antibodies (anti-CD40L mAbs) was unable to induce indefinite allograft survival. CTLA-4-immunoglobulin fusion protein (CTLA-4Ig) or anti-CD40L monotherapy only marginally prolonged xenograft survival; the combination of human CTLA-4Ig and anti-CD40L significantly prolonged xenograft survival (74 days), while the combination of murine CTLA-4Ig and anti-CD40L resulted in graft survival of >,120 days. CTLA-4Ig or anti-CD40L monotherapy or the combination of these agents inhibited the production of alloAbs, including anti-Gal Abs. CTLA-4Ig or anti-CD40L monotherapy partially controlled xenoAb and anti-Gal Ab production, while the combination was more effective. These observations corroborate our previous observations that humoral, including anti-Gal Ab, responses and rejection following allograft or concordant xenograft transplantation in GT-Ko mice are T-cell dependent and can be controlled by costimulation blockade. [source] Treatment of ANCA-associated systemic small-vessel vasculitisAPMIS, Issue 2009DAVID JAYNE Much has been learnt over the last 30 years to optimize the use of immunosuppressive and glucocorticoid therapies that has allowed the publication of treatment guidelines. However, major unmet needs remain in the treatment of ANCA-associated vasculitis (AAV) and include refractory disease, only partial efficacy and toxicity of current drugs and the need for long-term regimens. Newer therapies, including mycophenolate mofetil, leflunomide and rituximab, are providing a real opportunity for improved outcomes of AAV in the future. The development of therapy has been facilitated by international clinical research networks but delayed by the complexities of studying an uncommon, multi-system disease. [source] Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase,positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease modelsARTHRITIS & RHEUMATISM, Issue 2 2009Nicole R. Bianco Objective We have demonstrated previously that dendritic cells (DCs) modified with immunosuppressive cytokines, and exosomes derived from DCs can suppress the onset of murine collagen-induced arthritis (CIA) and reduce the severity of established arthritis. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that is important for immune regulation and tolerance maintenance. DCs expressing functional IDO can inhibit T cells by depleting them of essential tryptophan and/or by producing toxic metabolites, as well as by generating Treg cells. This study was undertaken to examine the immunosuppressive effects of bone marrow (BM),derived DCs genetically modified to express IDO, and of exosomes derived from IDO-positive DCs. Methods BM-derived DCs were adenovirally transduced with IDO or CTLA-4Ig (an inducer of IDO), and the resulting DCs and exosomes were tested for their immunosuppressive ability in the CIA and delayed-type hypersensitivity (DTH) murine models. Results Both DCs and exosomes derived from DCs overexpressing IDO had an antiinflammatory effect in CIA and DTH murine models. The suppressive effects were partially dependent on B7 costimulatory molecules. In addition, gene transfer of CTLA-4Ig to DCs resulted in induction of IDO in the DCs and in exosomes able to reduce inflammation in an IDO-dependent manner. Conclusion These results demonstrate that both IDO-expressing DCs and DC-derived exosomes are immunosuppressive and antiinflammatory, and are able to reverse established arthritis. Therefore, exosomes from IDO-positive DCs may represent a novel therapy for rheumatoid arthritis. [source] Effects of low-dose ultraviolet radiation on in vivo human cutaneous recall responsesAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2001Diona L Damian SUMMARY Relatively few studies have examined the effects of low-dose ultraviolet (UV) radiation on in vivo human cutaneous immunity, or the ability of sunscreens to prevent UV-induced immunosuppression. We have studied the effects of solar-simulated UV radiation on nickel contact hypersensitivity (CHS) in nickel-allergic volunteers, and on delayed type hypersensitivity responses in Mantoux-positive volunteers. Nickel CHS and Mantoux responses were significantly suppressed by acute, suberythemal UV exposures equivalent to less than 8 min summer sunlight. Both UVA and UVB wavebands were immunosuppressive, but UVA-induced immunosuppression was transient, whereas UVB had a more sustained effect. Dose,responses for UV immunosuppression were determined using the nickel method, enabling calculation of in vivo sunscreen immune protection factors in a manner analogous with sun protection factor measurement. Sunscreens were found to confer significantly less protection against UV-induced immunosuppression than against UV-induced erythema. [source] Optimizing the frequency of outpatient short-contact dithranol treatment used in combination with broadband ultraviolet B for psoriasis: a randomized, within-patient controlled trialBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2003S.R. Mcbride Summary Background Recent concerns over the side-effects of psoralen plus ultraviolet (UV) A, immunosuppressive and cytotoxic treatments have led to increased interest in dithranol for treatment of psoriasis. Few studies have investigated how frequently dithranol should be applied. Dithranol-induced inflammation is maximal at 48,72 h, suggesting that daily application of dithranol may not be optimal. Objectives To investigate the effectiveness of five times weekly application of short-contact dithranol (SCD) compared with three times weekly application in a dedicated hospital outpatient treatment unit. Methods A randomized, within-patient, controlled study was performed. Patients had SCD applied five times weekly to one half of the body, and three times weekly to the other side. Whole-body UVB irradiation was given 5 days a week. Patients were assessed weekly for 8 weeks. Principal outcome measures were percentage reduction in modified Psoriasis Area and Severity Index (mPASI) at the end of study and time to 50% improvement in mPASI score. Results Twenty-nine patients were recruited; four were excluded from analysis. Mean percentage reduction in mPASI score at the end of study for five times weekly application was 57·3% (95% confidence interval, CI 39·6,75·0%) and for three times weekly application was 55·4% (95% CI 37·8,73·1%; P = 0·34). Mean time to 50% improvement in mPASI for five times weekly treatment was 4·1 weeks and for three times weekly treatment was 4·0 weeks (P = 0·50). There was no difference in the frequency or severity of burning episodes for each side. Conclusions This study suggests that three times weekly application of SCD may be as effective as five times weekly when used in conjunction with UVB administered five times weekly. Large studies of whole-body comparisons are warranted to assess further the optimal frequency of SCD and UVB therapy for psoriasis. [source] | |||||||||||||||||||||||||||||||||||||