Comparative Studies on the Effects of Interleukin-4 and Interleukin-13 on Cytokine and Prostaglandin E2 Production by Amnion-derived WISH Cells

Authors

  • Jeffrey A. Keelan,

    Corresponding author
    1. Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, Auckland, New Zealand
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  • Timothy A. Sato,

    1. Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, Auckland, New Zealand
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  • Murray D. Mitchell

    1. Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, Auckland, New Zealand
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Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, Private Bag 92019, Auckland, New Zealand.

Abstract

PROBLEM: In hematopoietic cells, interleukin (IL)-13 shares many actions with IL-4. The effects of IL-13 in gestational tissues have yet to be reported, however. We compared the effects of IL-4 and IL-13 on the production of cytokines and prostaglandin E2 (PGE2) in epithelial amnion-derived WISH cells.

METHOD OF STUDY: WISH cells were treated with IL-4 or IL-13 (0.08–10 ng/ml) with/without cotreatment with IL-1β (0.2 ng/ml), tumor necrosis factor-α (10 ng/ml) or epidermal growth factor (5 ng/ml). The production of IL-6, IL-8, and PGE2 was measured by immunoassay after 16 hr.

RESULTS: Both IL-4 and IL-13 inhibited PGE2 production with indistinguishable concentration-response curves, under basal or stimulated conditions. The maximal inhibition of IL-1β-stimulated PGE2 production (to 28% ± 10% of control) was seen at 10 ng/ml of IL-4 or IL-13. Basal IL-6 production was stimulated approximately twofold by IL-4 and IL-13, whereas IL-4 and IL-13 both inhibited cytokine-stimulated (but not basal) IL-8 production by approximately 50%. In the presence of 1 ng/ml of IL-4, IL-13 was unable to further inhibit PGE2 production.

CONCLUSIONS: The inhibition of PGE2 and IL-8 production by IL-4 in WISH cells is mimicked by IL-13. Both cytokines, probably through binding to a common receptor complex, may share a role in suppressing inflammatory reactions within intrauterine tissues.

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