Am. J. Respir. Crit. Care Med., Volume 159, Number 5, May 1999, 1592-1599

Interleukin-8 Induces Lymphocyte Chemotaxis into the Pleural Space
Role of Pleural Macrophages

ELISABETTA PACE, MARK GJOMARKAJ, MARIO MELIS, MIRELLA PROFITA, MARIO SPATAFORA, ANTONIO M. VIGNOLA, GIOVANNI BONSIGNORE, and CHRISTOPHER H. MODY

Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo; Istituto di Medicina Generale e Pneumologia, Università degli Studi, Palermo, Italy; and Division of Pulmonary Medicine, University of Calgary, Calgary, Alberta, Canada

The pleural space is a potential compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells in a number of respiratory diseases. In an attempt to understand one aspect of the inflammatory process in the pleural space, we compared the responses in three different diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and TB effusions, but not in CHF. Surprisingly, the concentration of IL-8 correlated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer patients expressed IL-8, whereas IL-8 could not be detected from the cells of TB and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture supernatants from stimulated pleural macrophages. Stimulated pleural macrophages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL-8 protein production, and this activity was abrogated by blocking tumor necrosis factor-. These findings suggest that soluble IL-8 is an important factor for the recruitment of lymphocytes into the pleural space, and that this cytokine is produced by both pleural structural and cancer cells after their activation by macrophage-derived, cytokine-mediated signals.

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