IL-1 beta, a major stimulator of hyaluronan synthesis in vitro of human peritoneal mesothelial cells: relevance to peritonitis in CAPD.

The effect of several different growth factors and cytokines on the synthesis of hyaluronan (HA) by human peritoneal mesothelial cells (HPMC) was investigated. Growth arrested HPMC synthesized low levels of HA, but co-culture with PDGF-bb, TGF-beta 1, TNF-alpha, and IL-6 at a concentration of 10 ng/ml all increased HA synthesis between two- to three-fold. At the same concentration IL-1 beta significantly increased the synthesis eight-fold (N = 3; P < 0.05). The effect of IL-1 beta was also dose- and time-dependent and could be totally negated with interleukin-1 receptor antagonist (IL-1 beta RcA). Non-infected and infected dialysate from patients receiving CAPD was also found to stimulate HA synthesis by HPMC. The levels found with non-infected fluid were 4 x 10(4) dpm/ml (N = 6) and 12.9 x 10(4) dpm/ml (N = 6; P < 0.002) and 8.7 x 10(4) dpm/ml (N = 6; P < 0.003) for infected fluid collected one and two days after the commencement of peritonitis. IL-1 beta RcA dramatically reduced the effect of infected but not non-infected dialysate. These results provide new insights into the manner in which HA synthesis is controlled in the mesothelium and suggest that IL-1 beta is a key cytokine in the inflammatory response in CAPD patients.