Differential roles of interleukin-18 (IL-18) and IL-12 for induction of gamma interferon by staphylococcal cell wall components and superantigens

The roles of endogenous cytokines induced by either intact staphylococcal m icroorganisms or staphylococcal exotoxins were examined using human whole-b lood cultures. To accomplish this, interleukin-18 binding protein (IL-1813P ) and tumor necrosis factor binding protein (TNFbp) were used to neutralize IL-18 and TNF, respectively, whereas an anti-IL-12 monoclonal antibody was used to neutralize IL-12 and the IL-1 receptor antagonist (IL-1Ra) was use d to block IL-1 receptors. Heat-killed Staphylococcus epidermidis and Staph ylococcus aureus, as well as the staphylococcal superantigens toxic shock s yndrome toxin-1 (TSST-1) and staphylococcus enterotoxin B (SEB) induced gam ma interferon (IFN-gamma) production. Staphylococcus spp.-induced productio n of IFN-gamma required the presence of endogenous IL-18, IL-12, and TNF. I n contrast, TSST-1-induced IFN-gamma was not significantly reduced in the p resence of IL-1813P, anti-IL-12 antibodies, IL-1Ra, or anti-TNFbp. SEB-indu ced IFN-gamma was significantly inhibited only by anti-IL-12 antibodies, in dicating that endogenous IL-18, IL-1, and TNF are not required for SEB-indu ced IFN-gamma. In conclusion, the mechanisms of IFN-gamma stimulation by in tact staphylococcal microorganisms and by exotoxins differ, and this is lik ely due to the different receptors which are triggered on the cell membrane s. In contrast to its role in the interactions between staphylococci and ho st cells, IL-18 does not appear to play a major role in superantigen-induce d IFN-gamma.