THE EFFECT OF AN INTERLEUKIN RECEPTOR ANTAGONIST (IL-1RA) ON COLONOCYTE EICOSANOID RELEASE

WE investigated whether an interleukin I receptor antagonist (IL-1ra) altered cellular release of prostanoids and leukotrienes in a transfor med colonic cell line (CACO-2) in the presence of proinflammatory stim uli. Cellular inflammation was induced by treatment with lipopolysacch aride (LPS) or the cytokine, interleukin 1 beta (IL-1(beta)). In a sep arate set of experiments, cells were pretreated with IL-1ra prior to e xposure to LPS or IL-1(beta). Prostaglandin E(2) and leukotriene B-4 ( LTB(4)) levels were quantified by ELISA assays. Both LPS and IL-1(beta ) exposure were noted to stimulate cellular PGE(2) release, a response which was significantly inhibited by IL-1ra treatment. Either stimula nt when administered alone failed to stimulate release of LTB(4). When administered after IL-1ra pretreatment however, both stimuli caused a significant increase in LTB(4) release. These results suggest that a cytokine receptor antagonist can selectively influence eicosanoid prod uction in this cell line. Furthermore, this study suggests that a IL-1 ra may have a future clinical role in the treatment of inflammatory di sorders of the colon which are intimately licked to enhanced eicosanoi d synthesis.