Interleukin-1 induces a shock-like state in rabbits: synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.
In addition to activating T and B lymphocytes, interleukin-1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 micrograms/kg) rapidly developed decreased systemic arterial pressure with the lowest levels after 50-60 min. Associated with the hypotension, systemic vascular resistance and central venous pressure fell while cardiac output and heart rate increased. These responses were prevented by intravenous ibuprofen given 15 minutes prior to the IL-1. A bolus injection of IL-1 plus a 2 hour infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters. Tumor necrosis factor (TNF) induced a more profound shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 microgram/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state. Ibuprofen prevented the hemodynamic, leukocyte and platelet changes induced by the low-dose cytokine combination. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, that the combination of IL-1 and TNF is more potent than either agent alone, and that cyclooxygenase products are involved in IL-1/TNF-mediated shock.
Dinarello
C A
CA
Department of Medicine, Tufts University, Boston, MA.
Okusawa
S
S
Gelfand
J A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007375:Interleukin-1 / Q000633:toxicity*; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity*; D012772:Shock, Septic / Q000139:chemically induced* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007052:Ibuprofen