Mesenteric Lymph Flow in Endotoxemic Guinea Pigs

Background: Lipopolysaccharide (LPS) is a structural component of the outer membrane of gram-negative bacteria. LPS activates the host cells, leading to the production and release of proinflammatory cytokines. Given the induction duration for the release of cytokines, the initial mechanisms that produce LPS action on a timescale of minutes are not fully understood. We studied the effect of initial LPS-induced action on the lymphatic system by measuring the time-dependent changes in mesenteric lymph flow in guinea pigs in vivo. In addition, we determined the leakage of plasma protein into the lymphatic system using Evans blue dye. Methods and Results: The mesenteric lymphatic vessel was cannulated with a polyethylene catheter. We administered drugs via a catheter in jugular vein. The control animals received vehicle intravenously (i.v.). The experimental group received 1 mg/kg or 10 mg/kg LPS i.v. Twenty minutes before injection of the vehicle or LPS, Evans blue dye (5mg/kg i.v.) was administered. Lymph output was measured every 20 min. The amount of Evans blue in the lymph was determined by spectrophotometry. The mesenteric lymph showed a steady flow rate of approximately 290 mu L/kg/20min. The lymph flow immediately increased after the administration of LPS and reached 3.4-fold and 7.4-fold after 1 h of 1mg/kg and 10 mg/kg LPS injection, respectively. The albumin content in lymph significantly increased in proportion to the increased lymph volume. Conclusions: These results suggest that the early increase in mesenteric lymph flow rate in guinea pigs produced by LPS is mediated by vascular hyperpermeability and plasma albumin leakage.