Interleukin‐18 plays a role in both the alum‐induced T helper 2 response and the T helper 1 response induced by alum‐adsorbed interleukin‐12

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Abstract
Summary: Previous studies have shown that the antigen‐specific T helper 2 (Th2) response induced by alum adjuvants is interleukin (IL)‐4 independent. As a role for IL‐18 in Th2 induction has recently been described, in addition to its role in enhancing Th1 responses, we have studied the Th2 response induced by ovalbumin (OVA) adsorbed to alum in wild‐type and IL‐18‐deficient mice. Our results indicate that while endogenous IL‐18 facilitates alum‐induced IL‐4 production, OVA‐specific immunoglobulin G1 (IgG1) and IgE production remain unaffected. Furthermore, antigen‐specific Th1 responses induced with alum/IL‐12‐adsorbed OVA were demonstrated to be highly IL‐18 dependent. Despite these observations, injection of BALB/c mice with exogenous IL‐18 adsorbed to alum/OVA did not alter IL‐4 or interferon‐γ production by T cells and had little effect on the relative production of IgG1/IgG2a antibody subclasses compared with alum/OVA inoculated mice. However, the previously described synergism between IL‐12 and IL‐18 in Th1 induction was evident as the Th1‐promoting activity of alum/IL‐12 against adsorbed OVA was greatly augmented by the coadministration of IL‐18. These results indicate that while alum‐induced IL‐18 can facilitate Th2 induction, the addition of exogenous IL‐18 cannot further enhance the alum‐induced Th2 response.