Bee venom, immunostimulant or immunosuppressor? Insight into the effect on matrix metalloproteinases and interferons

The current evidence has defined conflicting properties for bee venom. The goal of this study was to determine whether bee venom (BV) is an immunosuppressor or immunostimulant. The WEHI-164, HT-1080, and K562 cell lines were used for assaying toxicity, proliferative response, matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) activity, and interferon production. The Australian and Iranian BV (ABV and IBV) were used at concentrations of 0.025-1 mu g/ml in triplicate and 2-fold dilutions. MMP-2 and -9 activities were evaluated using the zymography method. The production of interferons (IFN-alpha and IFN-beta) were assessed using enzyme-linked immunoassay procedure. Our results show no significant difference between two sources of honeybee venom (ABV and IBV) when they are added to an identified cell line, whereas the response of various cell lines against BV could be different. The increasing amounts of ABV and/or IBV (between doses 0.025-0.5 mu g/ml) to human monocyte cell line (K562) exhibit a significant increase in proliferative response. Our data show that the immunomodulatory effect of ABV and/or IBV on MMP-2 and MMP-9 activity in both cell culture media, WEHI-164 and K562, is similar. The stimulatory effect of BV on MMP-2 and -9 activities is occurred between doses 0-0.05 mu g/ml. In contrast, the inhibitory effect of BV on these two MMPs is seen at concentrations of >0.05 mu g/ml. The ABV and/or IBV has no influence on IFN-alpha production in cell culture media, whereas adding the BV to K562 cell line could significantly increase the production level of IFN-beta only on day 8 posttreatment. We conclude that time- and dose-dependent response as well as the type of treated cell line could determine the immunosuppressive and/or immunostimulant property of bee venom that could be effective in future therapeutic strategies.