Effect of interleukin-2 on microvascular liquid and protein transport in the rat small intestine

Interleukin-2 (IL-2), a glycoprotein lymphokine derived from activated T-lymphocytes displays potent anti-cancer properties but its therapeutic use has been limited by generalized tissue swelling. To shed light on the mechanism underlying this potentially life-threatening edematogenic syndrome, recombinant IL-2 or an equal volume of control solution (excipient or 5% dextrose) was administered to 88 adult, male Sprague-Dawley rats. Initially, rats were injected with 50,000 Cetus units (equal to 300,000 I.U.) of IL-2 intraperitoneally, either one-time ("acute" rats) or every eight hours for two or seven days ("chronic" rats). Thereafter, under pentobarbital anesthesia, the main mesenteric lymph duct was isolated, incised, and measurements made of intestinal lymph flow (JV) and the total protein content and protein fractions in lymph (L) and plasma (P) (refractometry and agarose gel electrophoresis, respectively). Final measurements were also carried out after superior mesenteric vein constriction to assess filtration-independent L/P total protein "washdown." After IL-2, JV and protein clearance (JV x L/P) were increased (p less than 0.001) while lymph and plasma total protein content and protein fractionation were unchanged. Protein washdown was also maintained. These data are not only inconsistent with bulk "plasma leak" from damaged capillaries, but in conjunction with previously demonstrated increased cardiac output and reduced systemic vascular resistance after IL-2 administration, the findings favor augmented microvascular surface exchange area from increased capillary perfusion as the primary mechanism underlying increased transcapillary liquid and protein flux. This conclusion conforms to the rapid reversal of edema in patients after cessation of IL-2 therapy.