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Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E₂ critically depends on interleukin-2

Lookup NU author(s): Professor Catharien HilkensORCiD

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Abstract

Prostaglandin E2 (PGE2) favors T helper type 2 (Th2)-like cytokine secretion profiles in murine and human CD4+ T cells by inhibiting the production of the Th1-associated cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and up-regulating the production of the Th2-associated cytokines IL-4 and IL-5 in a dose-dependent way. However, the potent inhibition of IL-2 production by PGE2 seems to be in contrast with the simultaneous up-regulation of IL-4 and IL-5 production, because the induction of these cytokines requires IL-2. We, therefore, investigated to which extent the net modulatory effect of PGE2 is determined by the availability of IL-2. To this aim, we examined the effects of PGE2 on the cytokine secretion profiles of a panel of human Th0 clones upon stimulation via different activation pathways, resulting either in high or low IL-2 production. The differential modulation of Th1 and Th2 cytokines by PGE2 was observed only upon modes of stimulation resulting in high IL-2 production. When IL-2 production was low, PGE2 inhibited the secretion of all four cytokines. These different modulation patterns were directly related to the IL-2 availability, because (i) neutralizing antibody to IL-2 abrogated the up-regulatory effect of PGE2 on IL-4 and IL-5 secretion in experiments with high endogenous IL-2 levels, (ii) lack of differential cytokine modulation by PGE2 in conditions with low levels of endogenous IL-2 could be restored with exogenous IL-2, and (iii) cell viability was comparable in all conditions. These results demonstrate that the net modulatory effect of PGE2 on the cytokine secretion profile of T cells critically depends on the availability of IL-2. Since this parameter varies with the experimental conditions and the T cell population studied, this finding may explain why certain immune responses may be either up- or down-regulated by PGE2 under different conditions.

Publication metadata

Author(s): Hilkens CM, Vermeulen H, van Neerven RJ, Snijdewint FG, Wierenga EA, Kapsenberg ML

Publication type: Article

Publication status: Published

Journal: European Journal of Immunology

Year: 1995

Volume: 25

Issue: 1

Pages: 59-63

Print publication date: 01/01/1995

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley - VCH Verlag GmbH & Co.

URL: http://dx.doi.org/10.1002/eji.1830250112

DOI: 10.1002/eji.1830250112

Notes: 0014-2980 Journal Article

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