Interleukin 8: an autocrine growth factor for malignant mesothelioma

Interleukin 8 (IL-8) is a potent chemokine that also has a direct growth-potentiating effect on certain tumors. In the present study, we determined IL-8 levels in human malignant mesothelioma (MM) effusions and congestive heart failure pleural fluids. We also investigated antigenic IL-8 production by different MM cell lines, and we describe the role of IL-8 in the autocrine 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 standard culture methods. The bioactive IL-8 levels were measured in supernatants of cultured cells by ELISA, and the expression of cell-associated immunoreactive IL-8 was observed by immunohistochemistry. The proliferative activity was determined by thymidine ([3H]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 significantly higher levels of IL-8 in mesothelioma pleural fluids than congestive heart failure and a time-dependent increase in IL-8 levels in MM-1 and MM-2 cell supernatants during 96 h of incubation. IL-8 levels were nearly undetectable in MM-3 and MC cell line supernatants. In MM-1 and MM-2 cells, IL-8 caused a dose-dependent increase of [3H]thymidine incorporation to maximal levels of 46.3 +/- 3.6% and 12.3 +/- 1.6% (P < 0.001), respectively, when compared with serum-free medium as control. Neutralization of IL-8 significantly decreased proliferative activity of MM-1 and MM-2. IL-8 did not induce proliferative activity in MM-3 and MC cells. We conclude that IL-8 had a direct growth-potentiating activity in MMs.