Pro-inflammatory cytokines in lung and blood during steroid-induced Pneumocystis carinii pneumonia in rats

Abstract: To gain more insight into the role of cyto-kines in Pneumocys:is cannhi pneumonia (PCP) we followed pro-inflammatory cytokine profiles in rats with steroid-induced PCP at 2-week intervals. The cyto-kines measured were immunoreactive interleukin-1 3 (IL-13), bioactive interleukin-6 (IL-6), and tumor ne-crosis factor a (TNF-a). In vivo cytokine concentra-tions were determined in three compartments, i.e., bronchoalveolar lavage (BAL) fluid, lung homogenates, and plasma. Lipopolysaccharide (LPS)-stimulated cyto-kine production by alveolar cells and in whole-blood cultures was measured ex vivo. P carinii load and host inflammatory response, as determined by lung/body weight ratio and “indium-IgG biodistribution were monitored throughout developing PCP. IL-13 was el-evated in lung homogenates (600, range <20-1260 pg/mL) and 11.6 in BAL fluid (48, range <20-115 pg/mL), whereas the pro-inflammatory cytokine con-centrations were not increased in plasma. Thus in rats with PCP elevated pro-inflammatory cytokine concen-trations were found to be restricted to the lung corn-partments. Corticosteroids did not significantly influ-ence cytokine concentrations, but showed profound inhibitory effects on ex vivo cytokine production. The LPS-.stnnulated cytokine production by alveolar cells gradually decreased during the 6 weeks after the start of the steroid injections, whereas the production in whole blood cultures was immediately and completel