Naja Naja Atra Venom And Neurotoxin Inhibited Skin Allograft Rejection In Rats

Background: Recent studies reported that Naja naja atra venom(NNAV) regulated immune function and had a therapeutic effect on adjunctive arthritis and nephropathy. We hypothesized that NNAV and its active component neurotoxin(NTX) might inhibit skin allograft rejection.Methods: Rat skin allograft was used to induce immune rejection in rats. In addition, mixed lymphocyte culture(MLC) was used to mimic immune rejection reaction in vitro. NNAV and NTX were given by oral 5 days prior to skin allograft surgery.Results: The results showed that oral administration of NNAV or NTX prolonged the survival of skin allograft and inhibited inflammatory response. The production of Th1 cytokines(IFN-γ, IL-2) was also suppressed. NTX inhibited T-cell proliferation and CD4+ T cell division induced by skin allograft. NTX also showed the immunosuppressive activity in mixed lymphocyte culture. The atropine alone inhibited Con A-induced proliferation of T cells, and potentiated NTX’ s inhibitory effects on T cells; while pilocarpine only slightly enhanced Con A-induced T cell proliferation, and partially reversed the inhibitory effect of NTX. On the other hand, Neither nicotine nor mecamylamine had an influence on NTX’s inhibitory effects on Con A-induced T cell proliferation in vitro assays. NTX inhibited T cell proliferation by arresting cell cycle at G0/G1 phase.Conclusions: The present study revealed that NNAV and NTX suppressed skin allograft rejection by inhibiting T cell-mediated immune responses. These findings suggest a potential role of NNAV and NTX as immune depressant agents for the treatment of relatively mild immune rejection induced by skin graft transplantation.