INTERLUEKIN-1-ALPHA, INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA INCREASE THE SYNTHESIS AND EXPRESSION OF THE FUNCTIONAL ALTERNATIVE AND TERMINAL COMPLEMENT PATHWAYS BY HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLSIN-VITRO

The proinflammatory cytokines interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) modulate th e synthesis of complement factors B and C3 by endothelial cells (EC), and are considered to play an important role in the development of sep sis. By using agarose beads activating the alternative pathway of comp lement, we wanted to study the net effect of these cytokines on EC syn thesis of the alternative and terminal pathways, measured by binding o f anti-C3c and anti-TCC (terminal complement complex) antibodies to be ads kept with the EC. Addition of IL-1 alpha and TNF alpha at concentr ations of 50 and 100 U/ml resulted in a significant increase in bindin g of these antibodies to co-incubated beads, most pronounced for anti- C3c. IL-6 from 50-200 U/ml resulted in a stronger (two to fourfold) bi nding for both antibodies compared to experiments with IL-1 alpha and TNF. However, increased concentrations of IL-1 alpha (200 U/ml) and IL -6 (400 U/ml) resulted in a strong reduction in binding of anti-C3c an d anti-TCC antibodies to the co-cultured beads. This study indicates t hat proinflammatory cytokines upregulate the synthesis by EC of the fu nctional alternative and terminal pathways of complement.