Interleukin 2 acutely induces platelet and neutrophil-endothelial adherence and macromolecular leakage.
The acute effects of interleukin 2 (IL-2) were determined in the rat cremaster microcirculation model by intravital, light, and electron microscopy to better understand the pathophysiology of the IL-2-induced vascular leak syndrome. Four groups of rats were studied over a 2-h monitoring period. One group received 1 x 10(6) units of IL-2/kg i.v. (n = 10), while the remaining groups received IL-2 topically applied to the cremaster muscle in dosages of either 1 x 10(5) (n = 9), 1 x 10(6) (n = 5), or 3 x 10(6) (n = 5) units. Each group was compared with controls (n = 9). IL-2 administered i.v. acutely induced platelet and polymorphonuclear leukocyte-endothelial adherence and microvascular macromolecular leakage that occurred synchronous with the development of tachycardia, hypotension, tachypnea, and hypoxemia. Topically applied IL-2 induced similar microvascular alterations but without changes in hemodynamic and respiratory parameters, which suggests that microvascular alterations were not caused by IL-2-induced changes in hemodynamic parameters. Electron microscopy of cremaster muscle sections demonstrated platelet and neutrophil adherence to the endothelium and endothelial injury. We conclude that IL-2 (or a locally generated mediator) acutely induces platelet and neutrophil-endothelial adherence in the rat skeletal muscle microcirculation that is associated with the development of macromolecular leakage from the microcirculation.
Edwards
M J
MJ
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
Miller
F N
FN
Sims
D E
DE
Abney
D L
DL
Schuschke
D A
DA
Corey
T S
TS
D000287:Administration, Topical; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D007376:Interleukin-2