CYTOKINES IN HUMAN RENAL INTERSTITIAL FIBROSIS .1. INTERLEUKIN-1 IS APARACRINE GROWTH-FACTOR FOR CULTURED FIBROSIS-DERIVED KIDNEY FIBROBLASTS

We studied the role of interleukin-1 beta (IL-1 beta) and basic fibrob last growth factor (bFGF) in the proliferative response of transformed human renal interstitial fibroblast cell lines established from eithe r a kidney with glomerulonephritis and interstitial fibrosis or a norm al kidney in comparison to primary human foreskin fibroblasts. Growth of fibrosis-derived renal fibroblasts was inhibited in the presence of IL-1 receptor antagonist: (IL-1Ra) by 35% (P < 0.005), suggesting tha t these cells produce IL-1 and possess IL-1 receptors as part of parac rine growth. In contrast, spontaneous proliferation of fibroblasts der ived from a normal kidney or normal skin were not inhibited by IL-1Ra. In fibrosis-derived but not in normal renal cells, fibronectin synthe sis was increased 2.2-fold (P < 0.01) in the presence of IL-1Ra. Addit ion of exogenous IL-1 beta or bFGF stimulated proliferation of skin fi broblasts. In contrast, growth of fibrosis-derived renal fibroblasts w as stimulated by IL-1 beta and unchanged by bFGF. Growth of normal kid ney fibroblasts was unaffected by bFGF and inhibited by IL-1 beta. We conclude that compared to normal fibroblasts, fibrosis-derived renal f ibroblasts have a different cytokine-response profile, are IL-1-depend ent, produce IL-1 as a paracrine growth factor and do not proliferate to bFGF, a classical fibroblast growth factor.