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Science 11 May 1990:
Vol. 248. no. 4956, pp. 739 - 742
DOI: 10.1126/science.2139736
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Articles

Science, Vol 248, Issue 4956, 739-742
Copyright © 1990 by American Association for the Advancement of Science

articles

Regulation of alloreactivity in vivo by a soluble form of the interleukin-1 receptor

WC Fanslow, JE Sims, H Sassenfeld, PJ Morrissey, S Gillis, SK Dower, and MB Widmer

Immunex Corporation, Seattle, WA 98101.

In vitro studies have shown that cytokines are involved in the regulation of the immune response, but their role in vivo is less well defined. Specific cytokine antagonists enable the identification of particular cytokines involved in the response and offer a means for modifying it. Systemic administration of a soluble, extracellular portion of the receptor for interleukin-1 (sIL-1R) had profound inhibitory effects on the development of in vivo alloreactivity. Survival of heterotopic heart allografts was prolonged from 12 days in controls to 17 days in mice treated with sIL-1R. Lymph node hyperplasia in response to a localized injection of allogeneic cells was completely blocked by sIL-1R treatment. The inhibition was overcome by simultaneous administration of interleukin-1 (IL-1); thus, sIL-1R acts by neutralizing IL-1. These results implicate IL-1 as a regulator of allograft rejection and demonstrate the in vivo biological efficacy of a soluble cytokine receptor.


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