Neurotoxin from Naja naja atra venom inhibits skin allograft rejection in rats

Int Immunopharmacol. 2015 Sep;28(1):188-98. doi: 10.1016/j.intimp.2015.05.040. Epub 2015 Jun 10.


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: Skin allografts were used to induce immune rejection in rats. In addition, mixed lymphocyte culture (MLC) was used to mimic immune rejection reaction in vitro. Both NNAV and NTX were orally given starting from 5days prior to skin allograft surgery.

Results: The results showed that oral administration of NNAV or NTX prolonged the survival of skin allografts 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 allografts. NTX also showed immunosuppressive activity in mixed lymphocyte culture. 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. NTX inhibited T cell proliferation by arresting the cell cycle at the 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 both NNAV and NTX as potential immunosuppressants for preventing the immune response to skin allografts.

Keywords: Acetylcholine receptor; Acute rejection; Naja naja atra venom; Neurotoxin; Proliferation; Skin allograft; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Concanavalin A / pharmacology
  • Cytokines / metabolism
  • Elapid Venoms / therapeutic use*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / drug effects
  • Male
  • Neurotoxins / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Skin Transplantation*
  • Spleen / cytology
  • Spleen / drug effects


  • Cytokines
  • Elapid Venoms
  • Immunosuppressive Agents
  • Neurotoxins
  • Concanavalin A