TALC-INDUCED EXPRESSION OF C-C AND C-X-C CHEMOKINES AND INTERCELLULAR-ADHESION MOLECULE-1 IN MESOTHELIAL CELLS

Treatment of symptomatic carcinomatous pleural effusions is primarily directed at local palliation with a wide variety of sclerosing agents, of which talc is considered to be the most successful. The mechanism whereby talc achieves this effect is unknown. The objective of this st udy was to investigate whether talc stimulates pleural mesothelial cel ls (PMC) to release C-X-C and/or C-C chemokines and express adhesion m olecules that initiate and amplify the inflammatory process in the ple ural space. When PMC were challenged with talc in vitro, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels were increas ed (p < 0.001) both at the protein and the mRNA level as compared with unstimulated cultures. Talc-stimulated PMC culture supernatant showed chemotactic activity for neutrophils and monocytes. The chemotactic a ctivity of PMC culture supernatant was blocked by 44.2% with IL-8-spec ific antibody and by 55.7% with MCP-1-specific antibody, demonstrating that PMC-derived chemokines are bioactive. Talc also enhanced interce llular adhesion molecule-1 (ICAM-1) expression in PMC. The data demons trate that talc stimulates PMC to release chemokines and express adhes ion molecules that may play a critical role in pleurodesis.