MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA C-C CHEMOKINE IN PARAPNEUMONIC PLEURAL EFFUSIONS

Parapneumonic pleural effusions are associated with the presence of a variety of inflammatory cells whose influx into the pleural space is a ttributed to the presence of inflammatory cytokines. Macrophage inflam matory protein-1 alpha (MIP-1 alpha), an important mononuclear chemoki ne, plays a critical role in pulmonary parenchymal inflammatory diseas e, but its role in the recruitment and activation of mononuclear phago cytes in the pleural space is unknown. In this study we demonstrate th at complicated parapneumonic pleural effusions (empyema) and uncomplic ated parapneumonic pleural effusions contain significantly (P < .001) higher levels of MIP-la with higher numbers of mononuclear cells when compared with effusions resulting from malignancy and congestive heart failure. The MIP-1 alpha was biologically active and contributed 43% and 37% of the mononuclear chemotactic activity of complicated and unc omplicated parapneumonic pleural fluids, respectively. In vitro, human mesothelial cells, when stimulated with interleukin-1 beta (IL-1 beta ), tumor necrosis factor-alpha (TNF-alpha), or bacterial lipopolysacch aride (LPS), produced MIP-la. Northern blot analysis confirmed that bo th endogenous (Il-1 beta or TNF-alpha) and exogenous (LPS) factors ind uce MIP-1 alpha expression in mesothelial cells. Supernatants from act ivated mesothelial cells demonstrated chemotactic activity for mononuc lear cells. This activity was blocked by MIP-la antibody, indicating t hat the MIP-1 alpha released was biologically active. We conclude that in parapneumonic pleural effusions, MIP-1 alpha plays a major but not exclusive role in the recruitment of mononuclear leukocytes from the vascular compartment to the pleural space, and pleural mesothelial cel ls by production of MIP-la actively participate in this process.