The Regulatory Effects Of Naja Naja Atra Venom On Immune Activity

Objectives: To investigate the role of NNAV in regulation of immune response,and to explore the potential mechanism of the immunomodulatory effects of NNAV onimmune system.Methods: Carbon clearance test, serum C3level, NK cell activity, serum IgMantibody response to SRBC, DTH response induced by DNFB and the proliferation ofsplenocytes were used to investigate the effects of NNAV on innate and adaptiveimmune responses in healthy mice. T lymphocyte subsets in spleen, serum IgG andIgM concentration, H&E staining of spleen tissue were used to measure the effects ofNNAV on dexamethasone-induced immunosuppressed mice. Cell viabilitymeasurement, cell cycle assay, CD4and CD8T-cell division, the concentrations ofIFN-γ, IL-4and IL-17in cell cultural supernatant, and Th1, Th2, Th17celldifferentiation were measured to investigate the mechanisms of the immunomodulatoryeffects of NNAV.Results: In normal mice, NNAV at the dose of20μg/kg could significantlyincrease the phagocytic index α. NNAV at doses of20μg/kg and40μg/kg couldmarkedly increase the secretion of compliment C3. The activity of NK cells werestrengthened by NNAV (40μg/kg,80μg/kg) in a dose-dependent manner. NNAV (40μg/kg,80μg/kg) could increase both the production of anti-SRBC IgM in sera and theproliferation of B cells in a dose-dependent manner. NNAV at doses of40μg/kg and80μg/kg could inhibit the ear swelling induced by DTH response, and T cellproliferation rate was inhibited as well. In the dexamethasone-mediatedimmunosuppressed mice, NNAV at dose of80μg/kg decreased the percentage of CD4 and CD8T cells, furthermore, the inhibition on CD8T cells was more robust than thaton CD4T cells and finally resulted in the restoration of CD4/CD8towards the normallevel. NNAV (20μg/kg,40μg/kg) could recover the levels of IgG and IgM suppressedby dexamethasone, and the generation of GCs was restored as well. In the mechanisticexploration, NNAV at dose of80μg/kg could arrest cell cycle at G0/G1phase, andsuppressed CD4and CD8T cell divisions without any influence on the cell viability.NNAV increased the secretion of IFN-γ and IL-4, while decreased the production ofIL-17. It was also confirmed that NNAV enhanced Th1and Th2but inhibited Th17celldifferentiation.Conclusions: NNAV could enhance the innate and humoral immune responsesvia increasing the function of Th1and Th2cell subsets. The inhibitory effects ofNNAV on the immune system are mainly mediated by the suppression of Th17andCD8T cells.