Interleukin 8: An autocrine growth factor for malignant mesothelioma

Interleukin 8 (IL-8) is a potent chemokine that also has a direct growth-po tentiating effect on certain tumors. In the present study, we determined IL -8 levels in human malignant mesothelioma (MM) effusions and congestive hea rt failure pleural fluids. We also investigated antigenic IL-S production b y different MM cell lines, and we describe the role of IL-8 in the autocrin e growth regulation of MMs, Mesothelial (CRL-9444 = MC) and MM (CRL-2081 = MM-1, CRL-5915 = MM-2, and CRL-5820 = MM-3) cell lines were grown using sta ndard culture methods. The bioactive IL-I levels were measured in supernata nts of cultured cells by ELISA, and the expression of cell-associated immun oreactive IL-8 was observed by immunohistochemistry. The proliferative acti vity was determined by thymidine ([H-3]thymidine) incorporation and also by direct cell counts after incubation with varying concentrations of IL-8 in the presence/absence of specific polyclonal IL-8 antibody. We found signif icantly higher levels of IL-8 in mesothelioma pleural fluids than congestiv e heart failure and a time-dependent increase in IL-8 levers in MM-1 and MM -2 cell supernatants during 96 h of incubation. IL-8 levels were nearly und etectable in MM-3 and MC cell line supernatants, In MM-l and MM-2 cells, IL -8 caused a dose-dependent increase of [H-3]thymidine incorporation to maxi mal levels of 46.3 +/- 3.6% and 12.3 +/- 1.6% (P < 0,001), respectively, wh en compared with serum-free medium as control. Neutralization of IL-8 signi ficantly decreased proliferative activity of MM-l and MM-2. IL-8 did not in duce proliferative activity in MM-3 and MC cells. We conclude that IL-8 had a direct growth-potentiating activity in MMs.