The ovarian action of interleukin-1 is receptor mediated: Reversal by a naturally occurring interleukin-1 receptor antagonist

E. Kokia, I. Ben-Shlomo, E. Y. Adashi

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19 Scopus citations


Objective: To address indirectly the possibility that the ovarian action(s) of interleukin (IL)-1 are receptor mediated and to re-examine the recently reported proposition that the naturally occurring IL-1 receptor antagonist (IL-1ra) may in fact act in the capacity of mixed IL-1 receptor agonist/antagonist. Design: In vitro treatment of isolated granulosa cell (GC) and whole ovarian dispersates of rat origin. Results: Treatment of GC from immature rats with increasing concentrations of IL-1ra (10 to 5,000 ng/mL) proved without effect on either the basal or FSH (100 ng/mL)-supported accumulation of P. Likewise, cellular viability (as assessed by conversion of 3-[4,5-dimethylthiazol-2-yl]-2-5 diphenyltetrazolium bromide to spectrophotometrically detectable formazan) remained unaltered. However, the concomitant addition of increasing concentrations of IL-1ra (10 to 5,000 ng/mL) yielded dose-dependent reversal of the 10 ng/mL IL-1β-mediated inhibition of the FSH-supported accumulation of P. Similarly, the ability of IL-1β to exert a dose-dependent (0 to 30 ng/mL) anti-gonadotropic effect was attenuated progressively given the concurrent presence of increasing concentrations (1,000 and 5,000 ng/mL) of IL-1ra. Although treatment of whole ovarian dispersates with 10 ng/mL IL-1β resulted in a 5.4-fold increase in the accumulation of prostaglandin (PG)E2, this effect too was all but eliminated after the concomitant addition of 5 μg/mL IL-1ra. Conclusions: These observations support the nontoxic nature of IL-1ra, confirm its lack of agonistic activity, validate its utility as an experimental probe, and suggest that neither the basal nor the FSH-stimulated accumulation of P are subject to regulation by endogenously produced GC-derived IL-1-like activity. Moreover, these observations suggest that the ability of IL-1β to inhibit the gonadotropin-supported accumulation of P and to increase PGE2 accumulation is receptor-mediated.

Original languageEnglish
Pages (from-to)176-181
Number of pages6
JournalFertility and Sterility
Issue number1
StatePublished - 1995
Externally publishedYes

Bibliographical note

Funding Information:
Received December 20, 1993; revised and accepted August 5, 1994. *Supported in part by National Institutes of Health Research grants HD-19998 and HD-30288 (E.Y.A.), and an American Physician Fellowship (E.K.). t On leave from the Rebecca Sieff Hospital, Safed, Israel. Recipient of an International Fellowship Award from the Israeli Medical Association, a Lalor Foundation Fellowship Award, and a Harlea Charitable Trust A ward.


  • Interleukin-1
  • granulosa
  • interleukin-1 receptor antagonist
  • ovary
  • prostaglandins


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