Interleukin-1-Induced Hypotension and the Effect of an Interleukin-1 Receptor Antagonist

  • C. A. Dinarello

Abstract

The systemic effects of high doses (> 1μg/kg) of intravenously administered interleukin (IL-1) in animals include hypotension, decreased systemic vascular resistance, depressed myocardial function, lactic acidosis, leukopenia, thrombocytopenia, vascular leak, pulmonary congestion, and tissue neutrophilic infiltration with necrosis [1, 2]. The hypotensive effects of intravenously administered IL-1 in humans have been observed at doses below 1 μg/kg, and hypotension is the major clinical response limiting the maximal dose tolerated to 300 ng/kg [3]. The hypotensive effect of IL-1 may occur via various mechanisms. One mechanism appears to be due to cyclooxygenase products, and IL-1 and tumor necrosis factor (TNF) act synergistically in increasing prostaglandin E (PGE) in a variety of cells. The hypotension following an IL-1/TNF injection in rabbits is blocked by cyclooxygenase inhibitors [1]. Arterial perfusion with IL-1 increases prostanoid synthesis, which lowers the pain threshold to bradykinin [4]. TNF potentiates these effects of IL-1. IL-1 inhibits vascular smooth muscle contraction, but this is independent of prostaglandin synthesis. The inhibition of smooth muscle contraction by IL-1 appears to be due to an L-arginine-dependent increase in nitric oxide production, which leads to increased guanylate cyclase activity [5, 6].

Keywords

Arthritis Leukemia Nitrite Oncol Polypeptide 

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Copyright information

© Springer-Verlag, Berlin Heidelberg 1993

Authors and Affiliations

  • C. A. Dinarello
    • 1
  1. 1.Department of MedicineTufts University and New England Medical CenterBostonUSA

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