ELEVATED LEVELS OF SHED TYPE-II IL-1 RECEPTOR IN SEPSIS - POTENTIAL ROLE FOR TYPE-II RECEPTOR IN REGULATION OF IL-1 RESPONSES

Two types of cellular IL-1Rs have been characterized and cloned from b oth human and murine sources. The type II IL-1R has a very short cytop lasmic domain and does not seem to participate in IL-1 signaling. We d emonstrate that type II IL-1Rs are released from the surface of neutro phils in response to treatment with TNF or endotoxin. In addition, ser um from patients with sepsis syndrome contains elevated levels of solu ble type II IL-1Rs. Neutrophils isolated from patients with sepsis hav e greatly enhanced expression of type II IL-1R mRNA and cell surface r eceptors and are therefore a likely source for the shed receptors in s erum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 bet a with highest affinity and also selectively inhibits IL-1 beta activi ty. We propose that increased cell surface expression and rapid releas e of preformed type II IL-1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulatin g IL-1 activity in sepsis.