IL-2 induces pulmonary edema and vasoconstriction independent of circulating lymphocytes.
We investigated the effect of IL-2 in the isolated guinea pig lung perfused with phosphate-buffered Ringer's solution (containing 0.5 g/100 ml albumin and 5.5 mM dextrose) to determine the mechanism of IL-2-induced pulmonary edema. IL-2 (0 to 10,000 U/ml) was added to the perfusate following a 10 min baseline steady-state period. Pulmonary arterial pressure (Ppa), pulmonary capillary pressure (Ppc), and change in lung weight (as a measure of developing pulmonary edema) were recorded at 0, 10, 30, 40, and 60 min. The capillary filtration coefficient (Kf.c), an index of vascular permeability to water, was measured at 30 and 60 min. Infusion of IL-2 increased Ppc (from 3.9 +/- 0.1 cm H2O at baseline to 8.8 +/- 1.1 cm H2O at 60 min for IL-2 at 2000 U/ml, p less than 0.01; and from 3.8 +/- 0.1 cm H2O at baseline to 8.9 +/- 0.6 cm H2O at 60 min for IL-2 at 10,000 U/ml, p less than 0.01. The lung weight also increased (32% at IL-2 concentration of 2000 U/ml, and 26% at IL-2 concentration of 10,000 U/ml) The capillary filtration coefficient did not change with IL-2 infusion. The IL-2 response was prevented using the pulmonary vasodilator, papaverine. The infusion of IL-2 was associated with the generation of thromboxane A2(TxA2) in the effluent perfusate. Inhibition of TxA2 synthetase using Dazoxiben prevented the pulmonary vasoconstriction and edema response to IL-2. In addition, IL-2 had no effect on the transendothelial clearance of 125I-albumin. The results indicate that IL-2 causes pulmonary edema secondary to an increase in Ppc. The response is mediated by IL-2 stimulation of TxA2 generation from the lung.
Ferro
T J
TJ
Department of Physiology, Albany Medical College, NY 12208.
Johnson
A
A
Everitt
J
J
Malik
A B
AB
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D011460:Prostaglandins F / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology* / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012711:Serum Albumin, Radio-Iodinated / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction
D007093:Imidazoles; D007376:Interleukin-2; D011460:Prostaglandins F; D012711:Serum Albumin, Radio-Iodinated; C029166:dazoxiben; D013929:Thromboxane B2; D010208:Papaverine; C100006:prostaglandin F1