CYTOKINE REGULATION OF MESOTHELIAL CELL-PROLIFERATION IN-VITRO AND IN-VIVO

Previous studies have demonstrated mitogenic effects of several mediat ors on mesothelial cells in vitro, but their effects in vivo have not been investigated. The aim of this study was to examine the effects of various cytokines on normal mesothelial cell proliferation in vitro a nd in vivo and correlate the findings in both assay systems. In vitro proliferation was assessed using a technique based on the uptake and s ubsequent release of methylene blue. Autoradiographic methods were app lied in a murine model to assess mitogenic activity of these factors o n mesothelium in vivo. In vitro data demonstrated a dose-dependent inc rease in human mesothelial cell proliferation by all mediators examine d: at optimal concentrations, proliferation was enhanced between 26.53 +/- 3.77 % standard deviation (SD), p < 0.001 for fibroblast growth f actor-2 (FGF-2) and 114.58 +/- 6.97 %, p < 0.001 for platelet-derived growth factor-AB (PDGF-AB) above control medium. In vivo, DNA synthesi s in mesothelial cells was stimulated by FGF-2 (29.52 +/- 5.85 % label ed cells, compared with 7.04 +/- 4.36 % for control medium; p < 0.001) , tumor necrosis factor-alpha (TNF-alpha; 13.14 +/- 4.55 % compared wi th 7.23 +/- 2.85; p < 0.005) and PDGF-BB (11.53 +/- 4.74 % compared wi th 4.67 +/- 3.48 %; p < 0.005). Transforming growth factor-beta(1) (TG F-beta(1)) and epidermal growth factor (EGF) had no effect on DNA synt hesis in mesothelial cells in vivo. It is concluded that FGF2, TNF-alp ha, and PDGF stimulate mesothelial cell proliferation in vitro and in vivo, whereas TGF-beta(1) and EGF only had a mitogenic effect in vitro at the concentrations examined. The mitogenic potency of the differen t PDGF isoforms in vitro was consistent with PDGF-alpha and beta recep tor expression.