Interleukin-1 Type II Receptor: A Decoy Target for IL-1 That Is Regulated by IL-4

Francesco Colotta(Mario Negri Institute for Pharmacological Research), Fabio Re(Mario Negri Institute for Pharmacological Research), Marta Muzio(Mario Negri Institute for Pharmacological Research), Riccardo Bertini(Mario Negri Institute for Pharmacological Research), Nadia Polentarutti(Mario Negri Institute for Pharmacological Research), Marina Sironi(Mario Negri Institute for Pharmacological Research), Judith G. Giri(Research & Development Corporation), Steven Dower(Research & Development Corporation), John E. Sims(Research & Development Corporation), Alberto Mantovani(Mario Negri Institute for Pharmacological Research)
Science
July 23, 1993
Cited by 982

Abstract

Interleukin-1 (IL-1) interacts with cells through two types of binding molecules, IL-1 type I receptor (IL-1R I) and IL-1R II. The function of IL-1R II is unknown. In studies using monoclonal antibodies, IL-1 prolonged the in vitro survival of polymorphonuclear cells (PMN) through IL-1R I, and IL-4 antagonized the action of IL-1 by inducing expression and release of IL-1R II. Dexamethasone also induced expression and release of the IL-1R II in PMN. These results, together with the effect of antibodies to IL-1R on IL-1-induced production of cytokines in monocytes, indicate that IL-1 acts on myelomonocytic cells through IL-1R I and that IL-1R II inhibits IL-1 activity by acting as a decoy target for IL-1. The existence of multiple pathways of regulation emphasizes the need for tight control of IL-1 action.


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