The effects of cytokines on suppression of lymphocyte proliferation by dexamethasone

Creed, Tom J., Lee, Richard W., Newcomb, Paul V., di Mambro, Alexandra J., Raju, Madhuri and Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462 2009. The effects of cytokines on suppression of lymphocyte proliferation by dexamethasone. The Journal of Immunology 183 (1) , pp. 164-171. 10.4049/jimmunol.0801998

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Abstract

Treatment failure occurs in up to 30% of patients treated with steroids for inflammatory diseases. The aim of this study was to explore the potential role of 21 cytokines in steroid-resistant inflammatory disease and to develop methods to restore steroid sensitivity through cytokine manipulation. The dexamethasone inhibition of lymphocyte proliferation assay correlates with the outcome of steroid therapy in ulcerative colitis (UC) and other inflammatory diseases. Using this assay, PBMC production of 21 cytokines, assayed by cytokine bead array, was correlated with percentage of suppression of proliferation by 10−6 M dexamethasone (Imax) in 26 healthy volunteers. Effects of the addition of exogenous cytokines to induce steroid resistance in PBMCs from healthy volunteers and cytokine blockade to improve steroid sensitivity in PBMCs from patients with steroid-resistant UC were then explored. Production of IL-1α, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF, TNF-α, and IFN-inducible protein 10 (IP-10) correlated significantly with in vitro steroid sensitivity; however, only IL-2 and TNF-α reduced steroid sensitivity when added exogenously. Addition of IL-10 enhanced steroid suppression. Immunoneutralization or receptor blockade of IL-2, but not TNF-α, IFN-γ, IL-4, IL-17, or IP-10 increased steroid sensitivity in cells from steroid-resistant UC patients. Neutralization of IL-10 reduced steroid sensitivity. Of the large panel of cytokines studied, IL-2 appears to have the greatest antagonistic effect on the antiproliferative effect of steroids. These data suggest that IL-2 inhibition in vivo may improve the response to steroids in steroid-resistant individuals.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	20 Oct 2022 08:47
URI:	https://orca.cardiff.ac.uk/id/eprint/29587

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