title: Human interleukin-27: wide individual variation in plasma levels and complex inter-relationships with interleukin-17A.
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.
authors: Immunity, Infection and Inflammation, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors: M A
authors: MA
authors: Forrester
authors: L
authors: L
authors: Robertson
authors: N
authors: N
authors: Bayoumi
authors: B D
authors: BD
authors: Keavney
authors: R N
authors: RN
authors: Barker
authors: M A
authors: MA
authors: Vickers
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D064094:Interleukin-27 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D064094:Interleukin-27
keywords: IL-17A; IL-27; T cells; cytokines; human