In interleukin‐4‐deficient mice, alum not only generates T helper 1 responses equivalent to Freund's complete adjuvant, but continues to induce T helper 2 cytokine production

Abstract

The role of interleukin (IL)‐4 in the activity of two frequently used vaccine adjuvants, Freund's complete adjuvant (FCA) and the aluminum hydroxide gels (alum), was studied using the standard antigen ovalbumin (OVA) in IL‐4 genedisrupted mice (IL‐4 ‐/‐). In the absence of adjuvant, there was an overall reduction in antibody production to OVA in IL‐4 −/− mice and significantly greater amounts of interferon (IFN)‐γ were produced following restimulation of splenocytes with antigen in vitro compared with immunocompetent controls (IL‐4 +/+). FCA and alum boosted the immune response to OVA in both IL‐4 −/− and IL‐4 +/+ mice. In IL‐4 +/+ mice, while FCA stimulated a wide‐spectrum immunoglobulin response, including both Th1‐associated IgG2a and Th2‐associated IgG1, alum enhanced only Th2 antibody production and no OVA‐specific IgG2a could be detected. In IL‐4‐deficient mice, however, not only was IgG2a production increased in all adjuvant‐treated groups, but alum was as potent at stimulating this antibody subclass as FCA. Similarly, increased production in vitro by splenocytes of the Th1 cytokine IFN‐γ, equivalent to that produced after inoculation with FCA/OVA, was only detected in IL‐4 −/− mice inoculated with alum/OVA. There was no IgE production in IL‐4 −/− mice and OVA‐specific IgG1 production, although still at significant levels, was reduced compared with wild‐type mice irrespective of the adjuvant used. However, although production of the Th2 cytokine IL‐5 was totally inhibited in IL‐4‐deficient mice inoculated with FCA/OVA, there was no significant difference in IL‐5 production between the two strains when alum was used as adjuvant.