The Role Of Cytokines In Acantholysis And Antibody Production Of Pemphigus

Objective: Pemphigus is an organ-specific autoimmune blistering skin disease, which specific auto-antibodies to keratinocyte desmosome component could be detected in serum. The disorders of cellular immunity and humoral immunity were found simultaneously exist in pemphigus patients in recent years. It is showed that there are signifcant inflammatory cell infiltration and abnormal cytokine levels in the lesion of pemphigus. The production of auto-antibody by B lymphocytes depends on the cooperation of CD4+ lymphocytes which action is restricted by HLA-II. All these studies suggested that Th2 lymphocytes were involved in pemphigus pathogenesis. In present study, we select two Th1 cytokines-- IL-2 and IFN-γ, one Th2 cytokine--IL-10 as our subjects and investigate their role in acantholysis and production of pemphigus antibody.Methods: Pemphigus autoantibodies were purificated from a patient with pemphigus vulgaris. The organ culture model of pemphigus in vitro was established. Acantholysis was observed histopathologically with interaction by different concentrations of IL-2, IFN-γand IL-10 at 24hr,48hr,72hr. After cell culture used EC1-2 ,EC4 and different concentrations of IL-2, IFN-γ,IL-10 to stimulate PBMC for seven days and detected the production of EC-specific IgG in culture supernatant with enzyme-linked immunoabsordent assay. Results: 1.Typical acanthoysis was observed in pemphigus skin organ culture model. 2.The acantholysis was promoted by IL-2 and IFN-γ,which severity of acantholysis was related to IL-2 and IFN-γ concentrations, and the effect of IFN-γwas weaker than that of IL-2. We also found that IL-10 could inhibit acantholysis induced by pemphigus antibody and IFN-γeffect significantly. IL-10 showed inhibitive effect to IL-2 at high concentration and promotive effect at low concentration. 3. All of IL-2, IFN-γ and IL-10 had the ability in stimulating the production of IgG by B lymphocytes which showed positive relation to their concentrations remarkably.Conclusions: Pemphigus auto-antibodies could induce typical acantholysis. The skin organ culture system was a good model to study the pathogensis of pemphigus in vitro. Th1cytokines could promote acantholysis, while Th2 cytokines showed inhibitive effect. Both types of cytokines could stimulate IgG secretion but IL-10 could not increase its role at high concentration. Our results suggest that Th2 cytokines could regulate the acantholysis and IgG secretion, and Th2 lymphocytes may play an important role at early stage in the pathogenesis of pemphigus.