Hypoglycemia, and Cytokine Release in D-Galactosamine-Sensitized and Unsensitized Mice

Administration of staphylococcal enterotoxin B (SEB) to BALB/c mice was found to induce a cytokine release syndrome hallmarked by weight loss and hypoglycemia. A neutralizing monoclonal antibody against gamma interferon (IFN-g) given before SEB counteracted weight loss and prevented hypoglycemia. This protective effect of anti-IFN-g antibody was associated with decreased IFN-g levels in serum; tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels remained unchanged. A monoclonal anti-IL-6 antibody, known for its ability to cause accumulation of biologically active IL-6 in the circulation, did not modify SEB-induced body weight loss or hypoglycemia. Levels of TNF, IFN-g, and IL-6 in serum were all more elevated in anti-IL-6-treated mice than in corresponding SEB-challenged control mice. In D-galactosamine-sensitized mice, SEB-induced weight loss but not hypoglycemia was more severe, resulting mostly in death within 24 h. Higher levels of biologically active TNF and IFN-g in serum were noted in these mice than in mice receiving SEB only. In D-galactosamine-sensitized mice, anti-IFN-g antibody did prevent hypoglycemia but failed to reduce the severity of the syn-drome. Again, TNF levels in anti-IFN-g-treated mice remained unchanged. Pretreatment with anti-IL-6 antibody temporarily attenuated SEB-induced hypoglycemia in sensitized mice. Thus, at 6 h post-SEB injec-tion, anti-IL-6-treated mice were less hypoglycemic than corresponding controls. However, at 24 h, hypogly-cemia was significantly aggravated. Concomitantly, IL-6 levels were dramatically increased. Neither anti-IFN-