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To gain more insight into the role of cytokines in Pneumocystis carinii pneumonia (PCP) we followed pro-inflammatory cytokine profiles in rats with steroid-induced PCP at 2-week intervals. The cytokines measured were immunoreactive interleukin-1beta (IL-1beta), bioactive interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). In vivo cytokine concentrations were determined in three compartments, i.e., bronchoalveolar lavage (BAL) fluid, lung homogenates, and plasma. Lipopolysaccharide (LPS) -stimulated cytokine 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 111indium-IgG biodistribution were monitored throughout developing PCP. IL-1beta was elevated in lung homogenates (600, range <20-1260 pg/mL) and IL-6 in BAL fluid (48, range <20-115 pg/mL), whereas the pro-inflammatory cytokine concentrations were not increased in plasma. Thus in rats with PCP elevated pro-inflammatory cytokine concentrations were found to be restricted to the lung compartments. Corticosteroids did not significantly influence cytokine concentrations, but showed profound inhibitory effects on ex vivo cytokine production. The LPS-stimulated 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 completely suppressed.

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Abstract. Concentrations and ex vivo production of interleukin 1b (IL-1), tumour necrosis a (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1b were increased in BAL fluid of HIV+ patients with PCP (184 Ϯ 47 pg mL -1 ) compared with undetectable levels in healthy control subjects (P = 0 . 0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2 . 1 Ϯ 0 . 7 vs. 0 . 5 Ϯ 0 . 2 ng mL -1 , P = 0 . 01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1 . 3 vs. 5 . 5 ng mL -1 , P = 0 . 009) and for IL-6 (0 . 6 vs. 2 . 5 ng mL -1 , P = 0 . 01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIVpatients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.