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Systemic Immune Responses (systemic + immune_response)
Selected AbstractsBacterial antigens alone can influence intestinal barrier integrity, but live bacteria are required for initiation of intestinal inflammation and injuryINFLAMMATORY BOWEL DISEASES, Issue 6 2006Beate C. Sydora PhD Abstract Intestinal flora plays a critical role in the initiation and perpetuation of inflammatory bowel disease. This study examined whether live fecal bacteria were necessary for the initiation of this inflammatory response or whether sterile fecal material would provoke a similar response. Three preparations of fecal material were prepared: (1) a slurry of live fecal bacteria, (2) a sterile lysate of bacterial antigens, and (3) a sterile filtrate of fecal water. Each preparation was introduced via gastric gavage into the intestines of axenic interleukin-10 gene-deficient mice genetically predisposed to develop inflammatory bowel disease. Intestinal barrier integrity and degrees of mucosal and systemic inflammations were determined for each preparation group. Intestinal barrier integrity, as determined by mannitol transmural flux, was altered by both live fecal bacterial and sterile lysates of bacterial antigens, although it was not altered by sterile filtrates of fecal water. However, only live fecal bacteria initiated mucosal inflammation and injury and a systemic immune response. Fecal bacterial antigens in the presence of live bacteria and sterile fecal bacterial antigens have different effects on the initiation and perpetuation of intestinal inflammation. [source] Serum IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis and healthy subjectsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2000A. C. R. Tanner Abstract Background/aims: Established periodontal diseases may be associated with antibody responses to periodontal pathogens, but it is not known at which stage of disease this antibody response is initiated. This study aimed to characterize the host systemic response in initial periodontitis, gingivitis, and periodontal health, to evaluate whether elevated serum antibodies to subgingival species could be detected in initial periodontitis. Method: Human systemic immune response were evaluated to 40 subgingival bacterial species in 16 healthy, 21 gingivitis, 11 initial periodontitis and 5 progressing recession adults. Subjects had minimal periodontal attachment level (AL) loss at baseline. Disease categories were determined after 12 months monitoring at three-month intervals. Increased AL loss 1.5 mm (disease activity) at interproximal sites defined initial periodontitis, recession was characterized by AL loss at buccal sites. Serum IgG antibodies were evaluated semi-quantitatively by immunoblot from blood taken at baseline, active and final visits. Results: No antibody was detected from 55% of reactions. When detected, levels were below those reported for advanced periodontitis subjects. There were no major differences in serum antibody levels between healthy, gingivitis and initial periodontitis subjects, despite differences in the subgingival microbiota. Serum antibodies for more species were detected in recession subjects, compared with the other study subjects. No changes in antibody levels were detected between baseline, active, and final visits. No systematic association between species colonization and presence of systemic antibody was observed. Conclusions: This study did not detect differential elevation of mean serum antibody levels in initial periodontitis subjects, suggesting that serum antibody levels are not sensitive risk markers for initial periodontitis. [source] Cellular inflammatory response to porcine collagen membranesJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2003Maria G. Patino Objectives:, The purpose of this study was to assess local inflammatory changes associated with the implantation of three different porcine collagen membranes having potential use in periodontal regeneration. Methods:, Materials were implanted subcutaneously into prepared sites along the dorsal skin surface of 60 female Wistar rats. Saline and turpentine were used as negative and positive controls, respectively. Animals were killed and biopsies obtained after 3 d, and at 1, 2, 4, 6, and 8 weeks after membrane implantation. A panel of six monoclonal antibodies was used to identify circulating monocytes (ED1), resident tissue macrophages (ED2), lymphoid macrophages (ED3), Ia-antigen expression (OX6), T-lymphocytes (OX19), and B-lymphocytes (OX33). Cells identified by each antibody were subjected to quantitative immunocytochemistry to compare any differences present among groups. Sera obtained 8 weeks after grafting were used in immunoblotting assays to detect the presence of systemic antiporcine antibodies. Results:, We found that the mononuclear cell subsets associated with implantation of porcine collagen membranes were similar to those obtained with saline administration. On the other hand, the use of turpentine resulted in an inflammatory infiltrate characterized by significantly higher numbers of all six monoclonal cell subsets at all time periods evaluated, compared to either saline or any of the membranes (P < 0.001). Conclusions:, The collagen membranes do not appear to be associated with a significant local inflammatory response, nor a systemic immune response, and thus appear to be well tolerated, rendering them useful in periodontal regeneration. [source] Electrolytic ablation is as effective as radiofrequency ablation in the treatment of artificial liver metastases in a pig modelJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2008Sebastian Hinz MD Abstract Background The best treatment option for liver metastases is complete surgical resection. Unfortunately, at the time of diagnosis, not all patients are candidates for complete resection. Electrolytic therapy (ECT) is a novel non-thermal method of tissue destruction. We evaluated its safety and effectiveness in comparison with radiofrequency ablation (RFA). Methods Tumor mimics were created by injecting a gel into the pig liver. The volume of the lesions was measured by ultrasound before treatment. The tumor mimics were treated with either RFA or electrolytic ablation. 48 h after treatment the liver was fixed in formalin and subjected to histological examination. Results Histological investigation confirmed that all lesions were completely surrounded by necrosis after treatment with either ECT or RFA. Two different types of necrosis were identified. After RFA the cell membranes disappeared but the nuclei were still intact, whereas after ECT these structures were completely disrupted. After ECT the necrosis was often surrounded by infiltrating lymphocytes. This inflammatory reaction was not apparent after RFA. Conclusion ECT produced predictable and reproducible necrosis in pig livers and was as effective as RFA at destroying a defined target lesion. A local inflammatory reaction after ECT may favour the development of a systemic immune response. Our results indicate that ECT is an alternative treatment option for irresectable liver metastases. J. Surg. Oncol. 2008;98:135,138. © 2008 Wiley-Liss, Inc. [source] Production of biopharmaceuticals and vaccines in plants via the chloroplast genomeBIOTECHNOLOGY JOURNAL, Issue 10 2006Henry Daniell Dr.Article first published online: 27 SEP 200 Abstract Transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation; heat stability; and absence of human pathogens. When therapeutic proteins are orally delivered, plant cells protect antigens in the stomach through bioencapsulation and eliminate the need for expensive purification and sterile injections, in addition to development of both systemic and mucosal immunity. Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance and multi-gene expression in a single transformation event. Hyper-expression of vaccine antigens against cholera, tetanus, anthrax, plague or canine parvovirus (4,31% of total soluble protein, tsp) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato), as well as the availability of antibiotic-free selectable markers or the ability to excise selectable marker genes, facilitate oral delivery. Hyper-expression of several therapeutic proteins, including human serum albumin (11.1% tsp), somatotropin (7% tsp), interferon-gamma (6% tsp), anti-microbial peptide (21.5% tsp), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitate assembly of complex multi-subunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLa cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner. [source] Local control of the immune response in the liverIMMUNOLOGICAL REVIEWS, Issue 1 2000Percy A. Knolle Summary: The physiological function of the liver , such as removal of pathogens and antigens from the blood, protein synthesis and metabolism , requires an immune response that is adapted to these tasks and is locally regulated. Pathogenic microorganisms must be efficiently eliminated while the large number of antigens derived from the gastrointestinal tract must be tolerized. From experimental observations it is evident that the liver favours the induction of tolerance rather than the induction of immunity. The liver probably not only is involved in transplantation tolerance but contributes as well to tolerance to orally ingested antigens (entering the liver with portal-venous blood) and to containment of systemic immune responses (antigen from the systemic circulation entering the liver with arterial blood). This review summarizes the experimental data that shed light on the molecular mechanisms and the cell populations of the liver involved in local immune regulation in the liver. Although hepatocytes constitute the major cell population of the liver, direct interaction of hepatocytes with leukocytes in the blood is unlikely. Sinusoidal endothelial cells, which line the hepatic sinusoids and separate hepatocytes from leukocytes in the sinusoidal lumen, and Kupffer cells, the resident macrophage population of the liver, can directly interact with passenger leukocytes. In the liver, clearance of antigen from the blood occurs mainly by sinusoidal endothelial cells through very efficient receptor-mediated endocytosis. Liver sinusoidal endothelial cells constitutively express all molecules necessary for antigen presentation (CD54, CD80, CD86, MHC class I and class II and CD40) and can function as antigen-presenting cells for CD4+ and CD8+ T cells. Thus, these cells probably contribute to hepatic immune surveillance by activation of effector T cells. Antigen-specific T-cell activation is influenced by the local microenvironment. This microenvironment is characterized by the physiological presence of bacterial constituents such as endotoxin and by the local release of immunosuppressive mediators such as interleukin-10, prostaglandin E2 and transforming growth factor-b. Different hepatic cell populations may contribute in different ways to tolerance induction in the liver. In vitro experiments revealed that naive T cells are activated by resident sinusoidal endothelial cells but do not differentiate into effector T cells. These T cells show a cytokine profile and a functional phenotype that is compatible with the induction of tolerance. Besides sinusoidal endothelial cells, other cell populations of the liver, such as dendritic cells, Kupffer cells and perhaps also hepatocytes, may contribute to tolerance induction by deletion of T cells through induction of apoptosis. [source] Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys?IMMUNOLOGY, Issue 1 2004Angela L. Man Summary Specialized microfold (M) cells of the follicle-associated epithelium (FAE) of the mucosal-associated lymphoid tissue (MALT) in gut and the respiratory system play an important role in the genesis of both mucosal and systemic immune responses by delivering antigenic substrate to the underlying lymphoid tissue where immune responses start. Although it has been shown that dendritic cells (DC) also have the ability to sample antigens directly from the gut lumen, M cells certainly remain the most important antigen-sampling cell to be investigated in order to devise novel methods to improve mucosal delivery of biologically active compounds. Recently, novel information on the interactions between bacteria and FAE have come to light that unveil further the complex cross-talk taking place at mucosal interfaces between bacteria, epithelial cells and the immune system and which are central to the formation and function of M cells. In particular, it has been shown that M cell mediated transport of antigen across the FAE is improved rapidly by exposure to certain bacteria, thus opening the way to identify new means to achieve a more effective mucosal delivery. Here, these novel findings and their potential in mucosal immunity are analysed and discussed, and new approaches to improve antigen delivery to the mucosal immune system are also proposed. [source] Airways infection with virulent Mycobacterium tuberculosis delays the influx of dendritic cells and the expression of costimulatory molecules in mediastinal lymph nodesIMMUNOLOGY, Issue 4 2004Gina S. García-Romo Summary Despite tuberculosis resurgence and extensive dendritic cell (DC) research, there are no in vivo studies evaluating DC within regional lymphoid tissue during airways infection with virulent Mycobacterium tuberculosis (Mtb) H37Rv. Using DC-specific antibodies, immunocytochemistry, flow cytometry and Ziehl,Neelsen (ZN) for bacilli staining, we searched for Mtb and DC changes within mediastinal lymph nodes, after intratracheal (ITT) inoculation of virulent Mtb. ZN and immunocytochemistry in frozen and paraffin sections of mediastinal lymph nodes identified Mtb until day 14 after ITT inoculation, associated with CD11c+ and Dec205+ DC. Analysing CD11c, MHC-CII, and Dec205 combinations by flow cytometry in MLN suspensions revealed that CD11c+/MHC-CII+ and CD11c+/Dec205+ DC did not increase until day 14, peaked on day 21, and sharply declined by day 28. No changes were seen in control, saline-inoculated animals. The costimulatory molecules evaluated in CD11c+ DCs followed a similar trend; the CD80 increase was negligible, slightly surpassed by CD40. CD86 increased earlier and the three markers peaked at day 21, declining by day 28. While antigen-specific proliferation was not evident for MLN CD4+ T cells at 2 weeks postinfection, delayed-type hypersensitivity responses upon ITT inoculation revealed that, as early as day 3 and 7, both the priming and peripheral systemic immune responses were clearly established, persisting until days 14,21. While airways infection with virulent Mtb triggers an early, systemic peripheral response maintained for three weeks, this seems dissociated from regional events within mediastinal lymph nodes, such as antigen-specific T-cell reactivity and a delay in the influx and local activation of DC. [source] Mechanisms of virus-induced asthma exacerbations: state-of-the-art.ALLERGY, Issue 5 2007A GA2LEN, InterAirways document Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] Salivary gland delivery of pDNA-cationic lipoplexes elicits systemic immune responsesORAL DISEASES, Issue 6 2002V Sankar OBJECTIVE: To test the ability of two cationic lipoplexes, Vaxfectin and GAP-DLRIE/DOPE, to facilitate transfection and elicit immune responses from plasmid DNAs (pDNAs) after retrograde instillation into salivary glands. METHODS: Two pDNA expression vectors encoding either the influenza NP protein or human growth hormone (hGH) were complexed with the cationic lipid transfection reagents, GAP-DLRIE/DOPE or Vaxfectin, and delivered to the submandibular glands of rats. Samples from rats receiving the influenza NP protein pDNA and cationic lipoplexes were analyzed for anti-influenza NP-specific IgG1, IgG2a, and IgG2b in serum, and IgA in saliva, by an enzyme- linked immunosorbent assay (ELISA). Cytotoxic T-cell lymphocyte (CTL) assays were also performed. Transgene protein expression (hGH) was determined from extracts of submandibular glands of rats receiving hGH lipoplexes. RESULTS: Serum antibodies (IgG) against the NP protein developed and were highest in all rats vaccinated with GAP-DLRIE/DOPE or Vaxfectin. The major serum IgG subclass stimulated by this route of immunization was IgG2b, followed by IgG2a. CTL assay results showed statistically significantly higher percentage killing in the Vaxfectin group than controls (P < 0.05). No rats developed IgA antibodies to NP protein in saliva. Animals receiving plasmid encoding hGH and either lipoplex expressed significantly higher amounts of hGH compared with those receiving the hGH plasmid and water. Although hGH expression was higher in the animals receiving pDNA/Vaxfectin (, 30-fold > pDNA/water), the difference with those receiving pDNA/GAP-DLRIE/DOPE (,10-fold > pDNA/water) was not significant. CONCLUSIONS: Retrograde instillation of pDNA complexed with Vaxfectin into the salivary glands can stimulate cytotoxic and humoral responses to the influenza NP protein antigen. Optimization of the conditions required to stimulate humoral and secretory antibody formation may facilitate use of this tissue for specific clinical applications of pDNA immunization. [source] CD4+ T cells mediate mucosal and systemic immune responses to experimental hookworm infectionPARASITE IMMUNOLOGY, Issue 6 2010B. DONDJI Summary Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4+ T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4+ for up to 9 days following intraperitoneal injection (200 ,g) of a murine anti-mouse CD4 monoclonal IgG (clone GK1·5). CD4+ T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4+ T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4+ T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4+ T-cell depletion, including HIV. [source] REVIEW ARTICLE: Effects of Early Conceptus Signals on Circulating Immune Cells: Lessons from Domestic RuminantsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Troy L. Ott Citation Ott TL, Gifford CA. Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants. Am J Reprod Immunol 2010 While there are few similarities between mechanisms for extending corpus luteum (CL) function during early pregnancy in ruminants and primates, there is increasing evidence that conceptus-immune crosstalk in ruminants and primates affects the function of circulating immune cells at the very earliest stages of pregnancy. Most notable are changes in immune cell phenotypes with increased numbers of cells exhibiting the T regulatory phenotype and suppression of Th1 cytokines that promote tolerance to paternal alloantigens. Until recently, interferon , produced by the ruminant trophectoderm was thought to act exclusively on the uterine endometrium; however, it is now clear that this unique embryonic interferon escapes the uterus and alters gene expression in the CL and in peripheral blood leukocytes (PBL). In fact, a large number of interferon-stimulated genes are now known to be increased during early pregnancy in PBL. What is not known is how this conceptus-immune system cross-talk affects maternal immune status outside the reproductive tract. It is attractive to hypothesize that some of these effects are designed to counter-balance progesterone-induced immunosuppression so as not to place the dam at a greater risk of infection on top of the tremendous stresses already induced by pregnancy. Furthermore, recent evidence suggests that pregnancy induced changes in peripheral immune cells may aid in orchestrating establishment of pregnancy. Existing evidence points toward a greater convergence of systemic immune responses to early pregnancy signaling between ruminants and primates. [source] Allergic Airway Hyperreactivity Increases the Risk for Corneal Allograft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009J. Y. Niederkorn Corneal allografts transplanted into hosts with allergic conjunctivitis experience an increased incidence and swifter tempo of immune rejection compared to corneal allografts transplanted to nonallergic hosts. Previous findings suggested that increased risk for rejection was not a local effect produced by an inflamed eye, but was due to perturbation of the systemic immune responses to alloantigens on the corneal allograft. We tested the hypothesis that another allergic disease, airway hyperreactivity (AHR), would also increase the risk for corneal allograft rejection. Induction of AHR with either ovalbumin (OVA) or short ragweed (SRW) extract prior to keratoplasty resulted in a steep increase in the speed and incidence of corneal allograft rejection. Delayed-type hypersensitivity (DTH) responses to corneal alloantigens were closely associated with corneal allograft rejection. However, the deleterious effect of AHR on corneal allograft survival was not reflected in a heightened magnitude of allospecific DTH, cytotoxic T lymphocyte and lymphoproliferative responses to the alloantigens on the corneal allograft. Unlike Th2-based immediate hypersensitivity, CD8+ T-cell-based contact hypersensitivity to oxazolone did not increase the risk for corneal allograft rejection. Thus, Th2-based allergic diseases significantly reduce the immune privilege of the corneal allograft and represent important risk factors for consideration in the atopic patient. [source] Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009K. Kulhankova Summary Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. Objective We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. Methods C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. Results Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG1, and IgG2a production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG1, lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. Conclusions Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures. [source] Cyclosporin A inhibits eosinophilic infiltration into the conjunctiva mediated by type IV allergic reactionsCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 4 2006Atsuki Fukushima MD Abstract Background:, Eosinophils are important effector cells in severe allergic conjunctivitis such as vernal keratoconjunctivitis. Infiltration of eosinophils into the conjunctiva is mediated by type I and type IV allergic reactions. Cyclosporin A (CsA) eye drops are administered therapeutically for severe allergic conjunctivitis, but the mechanism by which CsA acts, that is, by inhibiting type I, type IV or both types of allergic reactions, is not known. We investigated whether CsA eye drops inhibit type I, type IV or both types of allergic reactions in the conjunctiva. Methods:, Experimental immune-mediated blepharoconjunctivitis (EC) was induced in BALB/c mice by either active immunization or passive immunization by transfer of ragweed (RW)-primed splenocytes and RW-specific IgE, followed by RW challenge to the conjunctiva. These mice were treated in eye drops with vehicle, 0.1% CsA, 0.5% CsA or 0.1% betamethasone five times (1 and 2 h before RW challenge and 1, 2 and 3 h after RW challenge). Twenty-four hours after the challenge, the conjunctivas were harvested for histological analysis to evaluate eosinophilic infiltration. To evaluate effects of CsA eye drops on systemic immune responses, sera and spleens were collected from actively immunized mice at the time of sacrifice to examine serum IgE levels and cellular immune responses, respectively. Results:, CsA eye drops significantly inhibited eosinophilic infiltration into the conjunctiva in actively immunized EC-developing mice compared with vehicle-treated mice. The CsA-induced inhibition was similar to inhibition induced by 0.1% betamethasone. Serum IgE levels and splenocyte responses in CsA-treated mice were equivalent to those in vehicle-treated mice. Betamethasone treatment inhibited eosinophilic infiltration into the conjunctiva induced by both splenocyte transfer and IgE transfer, while CsA treatment inhibited infiltration induced by splenocyte transfer. Conclusions:, CsA eye drops inhibited eosinophilic infiltration into the conjunctiva without affecting systemic immune responses. CsA predominantly inhibits eosinophilic infiltration by interfering with the type IV allergic reaction in the conjunctiva. [source] | ||||||||||||||||||||||