Regulation of inhibitory pathways of the interleukin-1 system.

The IL-1 system includes two agonists, converting enzymes, antagonists, and two receptors (R). New elements and functions in the system will be discussed, including (a) cloning of a new isoform of the receptor antagonist; (b) further analysis of the type II IL-1-binding molecule as a decoy R. The modulation of IL-1R by chemotactic signals was recently investigated. It was found that chemoattractants cause rapid release of the type II decoy R from myelomonocytic cells with a t1/2 of 30 sec. Induction of decoy R release represents an early event in the multistep process of recruitment. It may serve to block the systemic action of IL-1 leaking from sites of inflammation, while preserving responsiveness in situ. We recently cloned the first long pentraxin, PTX3 (human and mouse, cDNA and genomic) as an IL-1-inducible gene. The structural and functional features of this molecule as well as initial evidence of involvement in human pathology will be discussed.