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Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A

Lookup NU author(s): Professor Bernard Keavney

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Abstract

Although it is widely believed that interleukin (IL)-27 is anti-inflammatory, its role in controlling human immune responses is not fully established. In particular, its interactions with T helper type 17 (Th) 17 cytokines are unclear. Our aims were to establish the relationships between IL-27 and proinflammatory cytokines, including IL-17A, in human sera and cultures of peripheral blood mononuclear cells. Plasma IL-27 levels in 879 healthy humans from 163 families varied widely, but with relatively low heritability (19%). Despite IL-27 including a subunit encoded by Epstein-Barr virus-induced gene 3 (EBI3), there was no correlation of levels with serological evidence of infection with the virus. Although IL-27 has been reported to inhibit IL-17A production, we demonstrated a strong positive correlation in sera, but lower correlations of IL-27 with other proinflammatory cytokines. We verified that IL-27 inhibited IL-17A production by human peripheral blood T cells in vitro, but not that it stimulated IL-10 secretion. Importantly, addition of IL-17A decreased IL-27 production by stimulated T cells but had the opposite effect on resting T cells. Together, these data suggest a model whereby IL-27 and IL-17A exerts complex reciprocal effects to boost inflammatory responses, but restrain resting cells to prevent inappropriate activation.

Publication metadata

Author(s): Forrester MA, Robertson L, Bayoumi N, Keavney BD, Barker RN, Vickers MA

Publication type: Article

Publication status: Published

Journal: Clinical & Experimental Immunology

Year: 2014

Volume: 178

Issue: 2

Pages: 373-383

Print publication date: 01/11/2014

Online publication date: 01/10/2014

Acceptance date: 22/06/2014

ISSN (print): 0009-9104

ISSN (electronic): 1365-2249

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/cei.12408

DOI: 10.1111/cei.12408

PubMed id: 24975574

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