EFFECT OF TUMOR-NECROSIS-FACTOR ON RAT INTESTINAL LYMPH DYNAMICS

The generalized edema that accompanies parenteral interleukin-2 treatm ent of patients for cancer is thought to be mediated by tumor necrosis factor (TNF). To examine this hypothesis, recombinant human TNF-alpha was administered intravenously to 8 anesthetized male Sprague-Dawley rats prepared with indwelling intestinal lymphatic and arterial cannul as. After determining lymph and blood parameters the superior mesenter ic vein (SMV) was narrowed to raise intestinal microvascular hydrostat ic pressure, and lymph flow and protein content further determined. Af ter TNF administration, intestinal lymph flow increased approximately 2 fold while the lymph and plasma total protein concentrations were un changed, effectively doubling lymph protein clearance. Blood hematocri t, mean arterial blood pressure and body temperature were also unchang ed after TNF. After SMV constriction, the phenomenon of lymph protein washdown (decreased or diluted lymph protein content) was maintained. The similarity of changes in intestinal lymph dynamics after TNF to th ose previously shown by us with IL-2 support mediation of the edematog enic syndrome through an IL-2/TNF pathway. Moreover, the lack of bulk loss of plasma with either agent (ie. lymph protein washdown effect is retained with raised microvascular hydrostatic pressure) suggests fur ther that increased protein clearance likely relates to recruitment of exchange vessels with greater surface area for leakage rather than co mpromise in microvascular integrity.