Bacterial lipopolysaccharide causes rapid shedding, followed by inhibitionof mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts

The IL-1 type I receptor (IL-1RI) is part of a signaling complex together w ith the IL-1R accessory protein, whereas available information is consisten t with a "decoy" model of function for the IL-1 type II receptor (IL-1RII). The present study was designed to investigate the effect of bacterial LPS on IL-1R in human monocytes, LPS causes rapid release of the IL-1RII, an ef fect blocked by a metalloprotease inhibitor. Subsequently, LPS-treated mono cytes showed a drastic reduction of IL-1RII mRNA, In contrast, LPS induced IL-1RI and, to a lesser extent, IL-1AcP expression. LPS-induced augmented e xpression of the canonical 5-kb IL-1RI mRNA was accompanied by the appearan ce of 2.4-kb IL-1RI transcripts, The use of probes representative of differ ent regions of the IL-1RI mRNA, as well as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely spliced, polyadenylated transcr ipts potentially encoding truncated versions of the receptor. The observati on that the prototypic proinflammatory molecule LPS has divergent effects o n IL-1Rs, with inhibition of IL-1RII and stimulation of IL-1RI and IL-1R ac cessory protein, is consistent with the view that these molecules subserve opposite functions in the pathophysiology of the IL-1 system. The rapid she dding of IL-1RII by monocytes early in recruitment may serve to buffer the systemic action of IL-1 leaking from sites of inflammation. This early even t, followed by prolonged inhibition of IL-1RII expression and up-regulation of IL-1RI, may render monocytes more responsive to IL-1 at sites of inflam mation.