REGULATION OF BOVINE INTERLEUKIN-1 RECEPTORS

Interleukin-1 is a key player in inflammation and the immune response. The interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL-1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies suggest a dynamic relationship among these receptors and ligands that regulates the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned and sequenced the bovin e type I and II interleukin-1 receptors, and has begun to investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI and IL-1RII mRNA levels were upregulated in vitro by various mediators, i ncluding dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Converse ly, IL-1RI mRNA levels were down-regulated by IFN-gamma. An in vivo st udy indicated that IL-1RII mRNA levels increased earlier than IL-1RI m RNA levels in dexamethasone-treated cattle. These findings suggest tha t early upregulation of IL-1RII, which is a decoy receptor, may be par t of the anti-inflammatory action of glucocorticoids. Our investigatio ns suggest that anti-inflammatory agents increase expression of the bi ologically inactive IL-1RII, as compared with the biologically active IL-1RI, in bovine leukocytes. (C) 1998 Elsevier Science B.V. All right s reserved.