In vivo biology of recombinant interleukin-2 infusion in sheep: cardiopulmonary manifestations of an intravascular immune-inflammatory response.
We have described the physiologic changes that occur in the conscious sheep during five days of dosing with rIL-2. Major effects noted were a decrease in systemic vascular resistance (vasodilation) accompanied by an increase in cardiac output (blood flow) and heart rate and a mild increase in pulmonary vascular resistance (vasoconstriction). Body temperature increased and may have contributed to the peripheral vasodilation. Lung microvascular fluid and protein flux increased following rIL-2 administration, as evidenced by an increase in lung lymph flow and protein clearance, and circulating levels of leukocytes decreased. These phenomena were temporally related. Since the composite biologic response that occurred following rIL-2 administration was characterized by changes in vascular caliber and blood flow, increased vascular permeability, and margination of leukocytes, we propose that the response be viewed as an intravascular inflammatory reaction.
Jesmok
G J
GJ
Department of Toxicology, Cetus Corporation, Emeryville, California 94608.
Gunther
R A
RA
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008196:Lymph / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D007376:Interleukin-2; D011994:Recombinant Proteins