title: Neither interleukin-6 nor signalling via tumour necrosis factor receptor-1 contribute to the adjuvant activity of Alum and Freund's adjuvant.
abstract: The potential contribution made by the inflammatory cytokines, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) to the adjuvant activity of aluminium hydroxide gels (Alum) or Freund's complete adjuvant (FCA) was studied by comparing the immunological responses of IL-6- or TNF receptor 1- (p55; TNFR-1) deficient mice with immunocompetent control mice. While both TNFR-1- and IL-6-deficient mice primed with ovalbumin (OVA) prepared in either Alum or FCA produced similar IgG.1 responses in comparison to control mice, the pattern of T-helper type 1- (Th1) dependent IgG2a production was significantly altered. In TNFR-1-deficient mice, IgG2a responses were greater than in control mice when FCA, but not when Alum, was used as an adjuvant. Correspondingly, spleen cells from FCA-inoculated TNFR-1-deficient mice restimulated with antigen in vitro produced higher Th1 cytokine (interferon-gamma; IFN-gamma) levels with no alteration in Th2 cytokine (IL-4; IL-5, IL-6 and IL-10) production in comparison with wild-type mice. Higher levels of IgG2a were also detected in IL-6-deficient mice compared with wild-type mice following inoculation with OVA prepared in either FCA or in Alum. Furthermore, analysis of cytokine production by spleen cells revealed that both Th1 and Th2 cytokine production was higher in IL-6-deficient mice compared with control mice. As the majority of the effects of TNF-alpha are mediated via TNFR-1, we conclude that this cytokine inhibits the adjuvant activities of FCA. Furthermore, the results also imply that immunopotentiating effects of FCA or Alum adjuvant are both inhibited by IL-6.
authors.affiliation: Department of Immunology, University of Strathclyde, Glasgow, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Brewer
authors.forename: M
authors.initials: M
authors.lastname: Conacher
authors.forename: M
authors.initials: M
authors.lastname: Gaffney
authors.forename: M
authors.initials: M
authors.lastname: Douglas
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: J
authors.initials: J
authors.lastname: Alexander
mesh_terms: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018929:Cell Culture Techniques; D005620:Freund's Adjuvant / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D007074:Immunoglobulin G; D015848:Interleukin-5; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D016753:Interleukin-10; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D005620:Freund's Adjuvant