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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.