INTERLEUKIN-8 AND EICOSANOID PRODUCTION IN THE LUNG DURING MODERATE TO SEVERE PNEUMOCYSTIS-CARINII PNEUMONIA IN AIDS - A ROLE OF INTERLEUKIN-8 IN THE PATHOGENESIS OF PNEUMOCYSTIS-CARINII PNEUMONIA

Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B-4 (LTB(4)) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A(2) (PLA(2)) and have been implicated in the host response to micro-organisms, Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant corticosteroids vs. placebo, in addition to standard antimicrobial therapy. Re-bronchoscopy was offered at day 10. BAL fluid was available for 26 patients who had follow-up bronchoscopy performed. At diagnosis, IL-8 levels were elevated in patients with PCP, compared to healthy controls, and correlated with relative BAL neutrophilia and P(A-a)O-2. LTB(4) was also elevated in PCP, but failed to correlate with either BAL neutrophilia or P(A-a)O-2. PLA, activity in patients correlated with IL-8 levels and BAL neutrophilia, but not with P(A-a)O-2. A trend towards a decrease in IL-8 levels in BAL fluid was detected in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB(4), LTC(4), PGE(2), PGF(2 alpha), and PLA(2) were detected over time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O-2, and suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear.