ANTI-GAMMA INTERFERON AND ANTI-INTERLEUKIN-6 ANTIBODIES AFFECT STAPHYLOCOCCAL-ENTEROTOXIN B-INDUCED WEIGHT-LOSS, HYPOGLYCEMIA, AND CYTOKINERELEASE IN D-GALACTOSAMINE-SENSITIZED AND UNSENSITIZED MICE

Administration of staphylococcal enterotoxin B (SEB) to BACB/c mice wa s found to induce a cytokine release syndrome hallmarked by weight los s and hypoglycemia, A neutralizing monoclonal antibody against gamma i nterferon (IFN-gamma) given before SEE counteracted weight loss and pr evented hypoglycemia, This protective effect of anti-IFN-gamma antibod y was associated with decreased IFN-gamma levels in serum; tumor necro sis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged, A monoclonal anti-IL-6 antibody, known for its ability to cause accumul ation of biologically active IL-6 in the circulation, did not modify S EE-induced body weight loss or hypoglycemia. Levels of TNF, IFN-gamma, and IL-6 in serum were all more elevated in anti-IL-6-treated mice th an in corresponding SEE-challenged control mice, In D-galactosamine-se nsitized mice, SEE-induced weight loss but not hypoglycemia was more s evere, resulting mostly in death within 24 h, Higher levels of biologi cally active TNF and IFN-gamma in serum were noted in these mice than in mice receiving SEE only, In D-galactosamine-sensitized mice, anti-I FN-gamma antibody did prevent hypoglycemia but failed to reduce the se verity of the syndrome, Again, TNF levels in anti-IFN-gamma-treated mi ce remained unchanged, Pretreatment with anti-IL-6 antibody temporaril y attenuated SEE-induced hypoglycemia in sensitized mice, Thus, at 6 h post-SEE injection, anti-IL-6-treated mice were less hypoglycemic tha n corresponding controls, However, at 24 h, hypoglycemia tvas signific antly aggravated, Concomitantly, IL-6 levels were dramatically increas ed, Neither anti-IFN-gamma nor anti-IL-6 antibody treatment modulated mortality levels in D-galactosamine-sensitized mice. The data obtained with anti-IFN-gamma antibody clearly indicate that endogenous IFN-gam ma is instrumental in bringing about hypoglycemia and body weight loss in mice exposed to SEE but also that hypoglycemia is not a crucial de terminant of mortality in D-galactosamine-sensitized mice. The data ob tained with anti-IL-6 antibody indicate that endogenous IL-6 is involv ed in regulating the levels of TNF and IFN-gamma in serum.