title: Interleukin-2 acutely induces protein leakage from the microcirculation.
abstract: Interleukin-2 has been shown to mediate the regression of metastatic cancer. However, therapeutic application has been limited by the induction of dose-dependent toxicities in normal tissues secondary to a vascular leak syndrome. To better understand the pathophysiology of this vascular leak syndrome, the earliest microvascular effects of interleukin-2 were directly observed and quantitated by intravital microscopy. The cremaster muscle of anesthetized Sprague-Dawley rats was prepared for in vivo microvascular observation. Animals were injected with fluorescein isothiocyanate-labeled albumin, and the interstitial emission intensity was used to assess macromolecular leakage. Both the intravenous injection and topical application of interleukin-2 to the cremaster muscle acutely induced the leakage of macromolecules from the microcirculation. The topical application of interleukin-2 induced macromolecular leakage without changes in central hemodynamic parameters. Furthermore, topically applied interleukin-2 did not produce changes in arteriolar or venular diameters, or in regional microvascular blood flow, which could have influenced the protein leakage. These data support the hypothesis that the acute increase in macromolecular leakage produced by interleukin-2 occurs secondary to an increase in endothelial porosity and not as a result of changes in hemodynamic or hydrostatic forces.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
authors.forename: M J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: D A
authors.initials: DA
authors.lastname: Schuschke
authors.forename: D L
authors.initials: DL
authors.lastname: Abney
authors.forename: F N
authors.initials: FN
authors.lastname: Miller
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000098:blood supply*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001798:Blood Proteins; D007376:Interleukin-2