title: 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)-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.
authors.affiliation: Department of Immunology, University of Strathclyde, Glasgow, Scotland.
authors.forename: J M
authors.initials: JM
authors.lastname: Brewer
authors.forename: M
authors.initials: M
authors.lastname: Conacher
authors.forename: A
authors.initials: A
authors.lastname: Satoskar
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: J
authors.initials: J
authors.lastname: Alexander
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D016207:Cytokines; D007074:Immunoglobulin G; D015847:Interleukin-4; C041524:aluminum sulfate; D010047:Ovalbumin; D005620:Freund's Adjuvant