Neither interleukin-6 nor signalling via tumour necrosis factor receptor-1 contribute to the adjuvant activity of Alum and Freund's adjuvant

Brewer, J.M. , Conacher, M., Gaffney, M., Douglas, M., Bluethmann, H. and Alexander, J. (1998) Neither interleukin-6 nor signalling via tumour necrosis factor receptor-1 contribute to the adjuvant activity of Alum and Freund's adjuvant. Immunology, 93(1), pp. 41-48. (doi: 10.1046/j.1365-2567.1998.00399.x) (PMID:9536117) (PMCID:PMC1364104)

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Abstract

The potential contribution made by the inflammatory cytokines, interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) 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 IgG1 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‐γ; IFN‐γ) 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‐α 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brewer, Professor James
Authors: Brewer, J.M., Conacher, M., Gaffney, M., Douglas, M., Bluethmann, H., and Alexander, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Blackwell
ISSN:0019-2805
ISSN (Online):1365-2567

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