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Immune Dysfunction (immune + dysfunction)
Selected AbstractsAlcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver DamageALCOHOLISM, Issue 10 2010Gyongyi Szabo Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source] Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Ehud Hauben Abstract Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults. [source] Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infectionFEMS YEAST RESEARCH, Issue 5 2010Brian M. Peters Abstract The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide. [source] Detection of endogenous lithium in neuropsychiatric disorders,a model for biological transmutationHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2002Ravi Kumar Kurup Abstract The human hypothalmus produces an endogenous membrane Na+ -K+ ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na+ -K+ ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na+ -K+ ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg++. The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na+ -K+ ATPase inhibition. The role of membrane Na+ -K+ ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na+ -K+ ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright © 2002 John Wiley & Sons, Ltd. [source] Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutininJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2007Nancy H. Augustine Abstract Lymphocyte proliferation in response to mitogens, phytohemagglutinin (PHA), concanavalin A, pokeweed, and/or specific antigens has been the method of choice for in vitro diagnosis of cell-mediated immune dysfunction. Recently, an assay to measure intracellular adenosine triphosphate (ATP) production in response to PHA has been developed that requires a shorter, overnight incubation. We compared a standard 5- to 7-day lymphocyte mitogen stimulation assay utilizing tritiated thymidine (3H-thy) incorporation to one in which ATP production in response to PHA by CD4-positive cells is measured in a luminometer that requires only 18,24,hr. A total of 20 patient samples suspected of having decreased cell-mediated immunity submitted for mitogen induced lymphocyte proliferation and 21 normal controls were tested in both assays. A comparison of these two methods has demonstrated that the screening ATP assay has a sensitivity at 24,hr of 100% in detecting decreased PHA induced lymphocyte proliferation at 5 days and a specificity of 85% in the samples obtained from normal controls. The data indicate that the ATP assay may be a useful screening tool for more rapid detection of blood samples with decreased cell-mediated immune responses. However, a positive screen should always be confirmed by 3H-thy uptake using mitogens and recall antigens like candida and tetanus. J. Clin. Lab. Anal. 21:265,270, 2007. © 2007 Wiley-Liss, Inc. [source] Multiple sclerosis in a radiosensitive family with low levels of the ATM proteinJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2002Raymond A Clarke SUMMARY Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system (CNS) characterized by demyelination associated with progressive disability. The mechanisms underlying the pathogenesis of MS remain a mystery. The highly pleiotropic syndrome known as ataxia telangiectasia (A-T) overlaps with MS in that it also presents with demyelination in the CNS. Whether demyelination in MS or in A-T is initiated through neuronal degeneration or immune dysfunction is not yet known. However, unlike MS, the underlying cause of A-T is known to result from mutations in the A,T gene (ATM) that often result in the complete loss of ATM protein and loss/gain of function. ATM is implicated in neurological degeneration, particularly in the cerebellum, cellular apoptosis, immunodeficiency, double stranded deoxyribonucleic acid (DNA) rejoining, VDJ antibody recombination, tumour suppression, particularly T-lymphoid malignancies, signal transduction, cell-cycle control and cellular radiohypersensitivity. In this study, we describe a case of MS in a family with cellular radiosensitivity and abnormally low postinduction levels of the ATM protein. Defective DNA repair/rejoining may impact on autoimmunity. [source] Mechanical Ventilation Exacerbates Alveolar Macrophage Dysfunction in the Lungs of Ethanol-Fed RatsALCOHOLISM, Issue 8 2005Pradip P. Kamat Background: Patients with alcohol abuse have a two- to three-fold increased risk of acute lung injury and respiratory failure after sepsis or trauma but are also at increased risk of nosocomial pneumonia. Mechanical ventilation exacerbates lung injury during critical illnesses. In this study we tested whether mechanical ventilation of the alcoholic lung promotes on balance a proinflammatory phenotype favoring ventilator-induced lung injury or an immunosuppressive phenotype favoring ventilator-associated pneumonia. Methods: Lungs from rats fed an isocaloric diet with or without ethanol (six weeks) were isolated and ventilated ex vivo with a low-volume (protective) or high-volume (injurious) strategy for two hours with or without prior endotoxemia (two hours). In other experiments, rats were subjected to high-volume ventilation in vivo. Airway levels of the proinflammatory cytokines tumor necrosis factor-,, macrophage inflammatory protein-2, and interleukin-1, were determined after mechanical ventilation ex vivo and compared with edematous lung injury after high-volume ventilation in vivo. In parallel, alveolar macrophage phagocytosis of bacteria and secretion of interleukin-12 during ventilation ex vivo and endotoxin-stimulated alveolar macrophage phagocytosis and tumor necrosis factor-, secretion in vitro were determined. Results: Ethanol ingestion suppressed the proinflammatory response to injurious mechanical ventilation and did not increase experimental ventilator-induced lung injury. In parallel, ethanol ingestion blunted the innate immune response of alveolar macrophages during injurious ventilation ex vivo and after endotoxin stimulation in vitro. Conclusions: Ethanol ingestion dampens ventilator-induced inflammation but exacerbates macrophage immune dysfunction. These findings could explain at least in part why alcoholic patients are at increased risk of ventilator-associated pneumonia. [source] The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantationLIVER TRANSPLANTATION, Issue 8 2002Raymund R. Razonable Human herpesvirus (HHV)-6 and -7 are novel members of the ,-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other ,-herpesvirus,cytomegalovirus (CMV). Coinfection among these three ,-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation. [source] Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airwaysALLERGY, Issue 10 2010T.-S. Shin To cite this article: Shin T-S, Kim JH, Kim Y-S, Jeon SG, Zhu Z, Gho YS, Kim Y-K. Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways. Allergy 2010; 65: 1256,1265. Abstract Background:, Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. Objective:, To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Methods:, Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 ,g of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. Results:, The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. Conclusion:, These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens. [source] Hypersensitivity and oral tolerance in the absence of a secretory immune systemALLERGY, Issue 5 2010M. R. Karlsson To cite this article: Karlsson M-R, Johansen F-E, Kahu H, Macpherson A, Brandtzaeg P. Hypersensitivity and oral tolerance in the absence of a secretory immune system. Allergy 2010; 65: 561,570. Abstract Background:, Mucosal immunity protects the epithelial barrier by immune exclusion of foreign antigens and by anti-inflammatory tolerance mechanisms, but there is a continuing debate about the role of secretory immunoglobulins (SIgs), particularly SIgA, in the protection against allergy and other inflammatory diseases. Lack of secretory antibodies may cause immune dysfunction and affect mucosally induced (oral) tolerance against food antigens. Methods:, We used polymeric Ig receptor (pIgR) knockout (KO) mice, which cannot export SIgA or SIgM, to study oral tolerance induction by ovalbumin (OVA) feeding and for parenteral antigen sensitization in the same animal. Results:, Remarkable systemic hyperreactivity was observed in pIgR KO mice, as 50% died after intradermal OVA challenge, which was not seen in similarly sensitized and challenged wild-type (WT) mice. Oral tolerance induced by OVA completely protected the sensitized pIgR KO mice against anaphylaxis and suppressed antibody levels (particularly IgG1) as well as delayed-type hypersensitivity (DTH) to OVA. Delayed-type hypersensitivity to a bystander antigen, human serum albumin, was also suppressed and T-cell proliferation against OVA in vitro was reduced in tolerized compared with non-tolerized pIgR KO mice. This effect was largely mediated by CD25+ T cells. Adoptive transfer of splenic putative regulatory T cells (CD4+ CD25+) obtained from OVA-fed pIgR KO mice to naïve WT mice mediated suppression of DTH against OVA after sensitization of the recipients. Conclusion:, Compensatory regulatory T-cell function becomes critical in pIgR-deficient mice to avoid the potentially catastrophic effects of systemic immune hyperreactivity, presumably resulting from defective secretory antibody-mediated immune exclusion of microbial components. [source] Children with frequent infections: A proposal for a stepwise assessment and investigation of the immune systemPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2010The immune defense to foreign invaders' Symphony. Cassimos DC, Liatsis M, Stogiannidou A, Kanariou MG. Children with frequent infections: A proposal for a stepwise assessment and investigation of the immune system. ,The immune defense to foreign invaders' Symphony. Which instrument is out of tune? Pediatr Allergy Immunol 2010: 21: 463,473. © 2009 John Wiley & Sons A/S Although many children develop frequent infections, only a few have an underlying immune disorder. Children with dysfunction of the immune system develop frequent infections and/or recurrent, persistent, severe, and rare infections. The aim of this review is to provide to the clinician a valuable tool for recognizing any ,discords' of the ,immune-system symphonic orchestra'. By following a reverse route, it will be possible to brighten up the dark and winding road of immunodeficiencies and identify the exact point of immune dysfunction. This is fundamental and crucial to perceive etiologic management and subsequently achieve the best for these young patients and their families. [source] Effect of L -arginine supplementation on immune responsiveness in patients with sickle cell disease,PEDIATRIC BLOOD & CANCER, Issue 2 2010Arnette Scavella MD Abstract Background L -arginine (L -Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L -Arg deficiency and immune dysfunction in SSD in steady-state. Procedure Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L -Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3,) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-,) were evaluated with and without L -Arg. Results SSD patients had significantly lower L -Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P,=,0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L -Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L -Arg supplementation did not increase this response. L -Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-, after addition of L -Arg. CD3, chain expression increased after addition of L -Arg in both groups; differences were insignificant. Conclusion L -Arg levels in steady-state SSD are significantly lower than in controls. L -Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3, chain expression although upregulation of expression occurred after L -Arg supplementation for both groups. Pediatr Blood Cancer. 2010;55:318,323. © 2010 Wiley,Liss, Inc. [source] Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis,THE JOURNAL OF PATHOLOGY, Issue 2 2009Pei-Chin Chuang Abstract Endometriosis, defined as the growth of endometrial tissues outside of the uterine cavity, is a severe and complex disease affecting more than 10% of women. The aetiology of endometriosis is unclear but immune dysfunction might be an important factor for its development. The natural function of the immune system is to detect and destroy aberrant or abnormal cells. Failure of the immune system to eradicate these aberrant cells often results in disease pathogenesis. We report here that the phagocytic ability of macrophages is reduced in peritoneal macrophages isolated from women with endometriosis. In-depth investigation revealed that the level of CD36, a class B scavenger receptor, in peritoneal macrophages derived from women with endometriosis was lower than that in normal macrophages. Blockage of CD36 function by neutralized antibody or knocking down CD36 using siRNA impaired the phagocytic ability of normal macrophages. In contrast, forced expression of CD36 in macrophages isolated from women with endometriosis restored phagocytic ability. Taken together, we identified that the scavenger receptor CD36 is reduced in the peritoneal macrophages of women with endometriosis, which leads to a decrease of the phagocytic ability of macrophages. These findings revealed a potential mechanism of immune dysfunction during endometriosis development. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosisARTHRITIS & RHEUMATISM, Issue 4 2009Patrizia Fuschiotti Objective T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell,derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc. Methods To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation. Results High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients. Conclusion Dysregulated IL-13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target. [source] Vitamin D discovery outpaces FDA decision makingBIOESSAYS, Issue 2 2008Trevor G. Marshall The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. BioEssays 30:173,182, 2008. © 2008 Wiley Periodicals, Inc. [source] Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia,reperfusion injuryBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2009P. J. Sullivan Background: Reperfusion injury (RI) has significant local and systemic consequences. Ischaemic preconditioning (IPC) modulates RI and the innate immune response. This study examined whether IPC attenuates RI-mediated changes in lymphocyte populations and function following elective surgery. Methods: Twenty-five patients sustaining 1 h of tourniquet ischaemia during cruciate ligament reconstruction were randomized before surgery to three 5-min ischaemia cycles separated by 5 min of reperfusion, or to a control group. Systemic levels of interleukin (IL) 4 and interferon (IFN) ,, and surface expression of CD45ro/ra, CD62L and CD95 were measured. T cells were examined systemically and in stimulated serum co-culture to determine CD4/CD8 and Th1/Th2 shifts through intracellular cytokine production. Results: CD4 CD45ro cell numbers increased after RI without IPC, whereas CD8 cells expressing CD45ro and CD95 increased with IPC. Preconditioned serum in co-culture attenuated increases in CD4 and decreases in CD8 numbers, a process prevented by inhibition of antigen activation. Following RI, systemic IL-2 levels were significantly lower after IPC, whereas co-culture with post-RI serum increased proinflammatory intracellular cytokine production. Conclusion: IPC modulated T cell responses in limb RI through reduced activation and proinflammatory cytokine production by CD4 cells, while preventing CD4/CD8 derangement. IPC prevented lymphocyte-directed immune dysfunction. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Peripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. A. R. Baker Summary Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (Treg) are CD4+ T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of Treg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of Treg in chronically infected, HIV-positive individuals over a course of 6 months. Treg are depleted at a distinct rate from that of absolute CD4 cells and loss of Treg is slower in the presence of viral suppression. In vitro depletion of CD25+ CD4+ cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of Treg and Gag-specific CD4 T cell responses was observed (r = ,0·41, P = 0·018) with a trend observed with Gag-specific CD8 T cell responses (P = 0·07). The impact of HIV infection on the Treg population directly complicates the measured effect of Treg on the immune dysfunction although our data support the important role of Treg on modulating the effector T cell response in chronic infection. [source] The keloid phenomenon: Progress toward a solutionCLINICAL ANATOMY, Issue 1 2007Louise Louw Abstract For centuries, keloids have been an enigma and despite considerable research to unravel this phenomenon no universally accepted treatment protocol currently exists. Historically, the etiology of keloids has been hypothesized by multiple different theories; however, a more contemporary view postulates a multifactoral basis for this disorder involving nutritional, biochemical, immunological, and genetic factors that play a role in this abnormal wound healing. Critical to the process of preventing or managing keloids is the need to locally control fibroblasts and their activities at the wound site. In recent years, considerable evidence has accumulated demonstrating the importance of fatty acids and bioactive lipids in health and disease, especially those involving inflammatory disorders or immune dysfunction. If hypertrophic scarring and keloid formation can be argued to have significant inflammatory histories, then it is possible to postulate a role for lipids in their etiology and potentially in their treatment. This report briefly visits past views and theories on keloid formation and treatment, and offers a theoretical rationale for considering adjuvant fatty acid therapy for keloid management. Sufficient scientific evidence in support of fatty acid strategies for the prevention and treatment of keloids currently exists, which offer opportunities to bridge the gap between the laboratory and the clinic. The intent of this paper is to serve as a basic guideline for researchers, nutritionists, and clinicians interested in keloids and to propose new directions for keloid management. Clin. Anat. 20:3,14, 2007. © 2006 Wiley-Liss, Inc. [source] Immune function in hypopituitarism: time to reconsider?CLINICAL ENDOCRINOLOGY, Issue 4 2010Annice Mukherjee Summary Hypopituitarism is not currently considered as a potential cause of immune disruption in humans. Accumulating data from in vitro and animal models support a role for the pituitary gland in immune regulation. Furthermore, the increased mortality risk noted in patients with adult hypopituitarism remains poorly explained and immune dysfunction could conceivably contribute to this observation. In a recent issue of Clinical & Experimental Immunology, we presented new data relating to immune status in adults with treated, severe hypopituitarism. We observed humoral immune deficiency in a significant proportion, despite stable pituitary replacement, including growth hormone (GH). This was especially evident in those with low pretreatment IGF-I levels and appeared independent of anticonvulsant use or corticosteroid replacement. These observations require substantiation with future studies. In this short review, we summarize existing data relating to the effects of pituitary hormones on immune function and discuss potential clinical implications surrounding the hypothesis of immune dysregulation in severe hypopituitarism. [source] | |||||||||||||