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

Eur J Immunol. 1996 Sep;26(9):2062-6. doi: 10.1002/eji.1830260915.

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)-gamma 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-gamma, 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.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Alum Compounds / pharmacology*
  • Animals
  • Cytokines / biosynthesis*
  • Female
  • Freund's Adjuvant / pharmacology*
  • Immunoglobulin G / biosynthesis
  • Interleukin-4 / deficiency
  • Interleukin-4 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Cytokines
  • Immunoglobulin G
  • Interleukin-4
  • aluminum sulfate
  • Ovalbumin
  • Freund's Adjuvant