Production of proinflammatory cytokines and adhesion molecules in ex-vivo xenogeneic kidney perfusion.

Abstract

Xenogeneic transplantation of solid organs is limited due to hyperacute rejection. In concordant systems, the mechanisms of rejection can be studied due to cross-reactivity of mediators with anti-human monoclonal antibodies. The aim of this study was to obtain information about the kinetics of proinflammatory cytokines and production of soluble adhesion molecules in the acute phase of reperfusion, eight kidneys from rhesus monkeys were perfused ex-vivo with human blood (group B/0) for 1 hour in a closed system. Blood levels of IL-1b, IL-6, TNFalpha, soluble ICAM, and E-selectin were measured using an ELISA technique under steady-state conditions. Cytokine levels rose significantly within the 60-min interval (IL-1b, 6.1 +/- 2.6-161.1 +/- 98.5 pg/ml; IL-6, 30.2 +/- 7.7-274.2 +/- 75.8 pg/ml; TNFalpha, 544.2 +/- 363.6-1651.0 +/- 25.7 pg/ml; P < 0.05). Immediately after the beginning of reperfusion, soluble ICAM-1 and selectin levels were abnormally high and rose constantly throughout the observation period, reaching significance at 60 min. High levels of proinflammatory cytokines may lead to an induction of adhesion molecules, thus, upregulating the leukocyte-endothelial interaction in a complement-independent mechanism. Specific pretreatment with monoclonal antibodies against ICAM-1, LFA-1, or other soluble mediators may be useful in down-regulating hyperacute rejection in trans-species transplantation.