INTERLEUKIN-8 IS A MAJOR NEUTROPHIL CHEMOTACTIC FACTOR IN PLEURAL LIQUID OF PATIENTS WITH EMPYEMA

Interleukin-8(IL-8),a potent neutrophil chemotactic peptide, has been found in association with human disease, but its contribution to chemotactic activity In humans is not yet known. We asked whether IL-8 is present in inflammatory human pleural effusions, and to what extent it contributes to pleural liquid neutrophil chemotactic activity. Because tumor necrosis factor alpha (TNF-alpha) is a strong inducer of IL-8, we also asked whether TNF-alpha was present. For this prospective study, we collected pleural liquid from 51 patients (empyema, 14; parapneumonic, four; tuberculous, eight; malignant, nine; miscellaneous exudative, seven; and transudative, nine), counted pleural neutrophils, and measured IL-8 and TNF-alpha concentrations in the supernatant. To determine the contribution of IL-8 to chemotactic activity in empyema, we measured the neutrophil migration induced by empyemic liquids before and after addition of anti-IL-8 F(ab')2 antibody fragments or control anti-IL-6 F(ab')2. We found that IL-8 concentrations were higher in empyema (61.3 +/- 21.0 ng/ml [SEM]) than in all other effusions (1.1 +/- 0.5 ng/ml) (p = 0.0001). All empyema liquids had IL-8 concentrations above 2.5 ng/ml, which was true for only three of the other 37 effusions (two parapneumonic, one tuberculous). IL-8 levels correlated with the pleural neutrophil count (r = 0.46; p = 0.007) and the neutrophil chemotactic activity of pleural liquid (r = 0.43; p = 0.008). Anti-IL-8 antibodies decreased chemotactic activity in empyema liquids by 65 +/- 5%, whereas the control antibody had no effect (0 +/- 5% decrease) (p = 0.0005). Although antigenic TNF-alpha was found most frequently in empyemic (79% of effusions) and tuberculous (88%) effusions, TNF bioactivity was detected only in empyemic (four of nine effusions), not in tuberculous effusions (zero of seven) (p = 0.044). We conclude that IL-8 represents a major neutrophil chemotactic factor in the pleural liquid of patients with empyema and that intrapleural TNF-alpha may participate in induction of IL-8 production.