Comparative studies on the effects of interleukin-4 and interleukin-13 on cytokine and prostaglandin E2 production by amnion-derived WISH cells.
OBJECTIVE
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.


METHODS
WISH cells were treated with IL-4 or IL-13 (0.08-10 ng/ml) with/without cotreatment with IL-1 beta (0.2 ng/ml), tumor necrosis factor-alpha (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-1 beta-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.
Keelan
J A
JA
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland School of Medicine, New Zealand.
Sato
T A
TA
Mitchell
M D
MD
D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D018793:Interleukin-13; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D004815:Epidermal Growth Factor; D015232:Dinoprostone