INTERLEUKIN-1-BETA STIMULATES HUMAN MESANGIAL CELLS TO SYNTHESIZE AND RELEASE INTERLEUKIN-6 AND INTERLEUKIN-8

Interleukin-1-beta (IL-1-beta) and tumor necrosis factor (TNF) have been reported to stimulate human mesangial cells (HMC) to proliferate and synthesize eicosanoids. We have examined whether they also induce HMC to release cytokines. In this study we show that both IL-1 and TNF stimulate HMC to release IL-6 and IL-8. Cycling and quiescent HMC were stimulated with various concentrations of either recombinant IL-1-beta or TNF for 1 to 24 hours. IL-1-beta at doses as low as 6 pg/ml stimulated mesangial cells to synthesize mRNA for both IL-6 and IL-8 as assessed by Northern analysis; mRNA for tubulin remained constant, which demonstrated a specific increase in mRNA. Secretion of IL-6 and IL-8 into the culture medium increased (4.5 to 18 ng/ml and 4 to 40 ng/ml, respectively) measured by ELISAs. TNF had similar effects but only in high concentrations (> 100 ng/ml). IL-1-beta did not stimulate cells to proliferate, as measured by H-3 thymidine incorporation. TNF caused proliferation but only in concentrations over 100 ng/ml. We conclude that IL-1-beta is a potent stimulator of human mesangial cell production of IL-6 and IL-8, both of which may influence injury in nephritis. TNF also stimulates mesangial cells but only in pharmacological doses.