IN INTERLEUKIN-4-DEFICIENT MICE, ALUM NOT ONLY GENERATES T-HELPER-1 RESPONSES EQUIVALENT TO FREUND COMPLETE ADJUVANT, BUT CONTINUES TO INDUCE T-HELPER-2 CYTOKINE PRODUCTION

The role of interleukin (IL)-4 in the activity of two frequently used vaccine adjuvants, Freund's complete adjuvant (FCA) and the aluminum h ydroxide gels (alum), was studied using the standard antigen ovalbumin (OVA) in IL-4 gene-disrupted mice (IL-4 -/-). In the absence of adjuv ant, there was an overall reduction: in antibody production to OVA in IL-4 -/- mice and significantly greater amounts of interferon (IFN)-ga mma were produced following restimulation of splenocytes with antigen in vitro compared with immunocompetent controls (IL-4 +/+). FCA and al um boosted the immune response to OVA in both IL-4 -/- and IL-4 +/+ mi ce. In IL-4 +/+ mice, while FCA stimulated a wide-spectrum immunoglobu lin response, including both Th1-associated IgG2a and Th2-associated I gG1, alum enhanced only Th2 antibody production and no OVA-specific Ig G2a could be detected. In IL-4-deficient mice, however. not only was I gG2a production increased in all adjuvant-treated groups, but alum was as potent at stimulating this antibody subclass as FCA. Similarly, in creased production in vitro by splenocytes of the Th1 cytokine IFN-gam ma, equivalent to that produced after inoculation with FCA/OVA, was on ly detected in IL-4 -/- mice inoculated with alum/OVA. There was no Ig E production in IL-4 -/- mice and OVA-specific IgG1 production, althou gh still at significant levels, was reduced compared with wild-type mi ce irrespective of the adjuvant used. However, although production of the Th2 cytokine IL-5 was totally inhibited in IL-4-deficient mice ino culated with FCA/OVA, there was no significant difference in IL-5 prod uction between the two Strains when alum was used as adjuvant.