Interleukin-1 (IL-1), a modulatory protein with immune and inflammatory functions, is spontaneously released by tissue macrophages in lower concentrations compared with peripheral blood monocytes. Conversely, in idiopathic pulmonary fibrosis, sarcoidosis, and certain inflammatory diseases, increased amounts of IL-1 are released by alveolar macrophages (AM). We examined IL-1 production by AM from patients with adult respiratory distress syndrome (ARDS) and compared it with that in patients with severe pneumonia requiring assisted ventilation, patients with pneumonia requiring parenteral antibiotics, and healthy control subjects. In vitro, ARDS AM released significantly more total IL-1 and IL-1 beta than did ARDS AM in patients with pneumonia and in control subjects. Moreover, after stimulation of these cells with 10 micrograms/ml of lipopolysaccharide (LPS), ARDS AM significantly increased release of IL-1 and IL-1 beta. AM from patients with severe pneumonia also released greater amounts of both IL-1 and IL-1 beta as fresh explants and after LPS stimulation when compared with control subjects. Incubation of AM with 250 U/ml human interferon-gamma (gamma IFN) was associated with less IL-1 beta release. However, stimulating AM from patients with ARDS and severe pneumonia with gamma IFN plus LPS enhanced the release of IL-1 beta compared with that in patients with pneumonia and in control subjects. ARDS AM released significantly more IL-1 beta than did all of the other groups. These results demonstrate that AM from patients with ARDS are capable of releasing significantly greater amounts of IL-1, which may be related to the progression of acute lung injury.

A bstract. We studied the interaction between Legionella pneumophila, which is principally a pulmonary pathogen, with primate alveolar macrophages (AM), which are the primary pulmonary cellular defense mechanism. For these studies we used L. pneumophila, type I, which were grown in albumin-yeast extract broth, were >80% viable, and were comparable in virulence for guinea pigs to organisms from guinea pig spleen homogenates. For comparison, avirulent agar-passed L. pneumophila, type I, and a strain of Escherichia coli were also used. In the absence of detectable antibody, AM phagocytosed similar numbers of virulent and avirulent Legionella and killed the majority of ingested Legionella in 15-30 min, as determined by two different assays. The virulent and avirulent Legionella appeared to be equally susceptible to the cidal systems ofthe AM and both were killed more readily than were E. coli under both assay conditions. Phagocytosis of Legionella by AM was associated with a localized respiratory burst, as indicated by nitroblue tetrazolium reduction around ingested organisms. Killing ofAM-associated Legionella was inhibited by the hydroxyl radical (OH * ) scavenger mannitol (but not by an equiosmolar concentration of sodium sulfate), and by a combination of superoxide dismutase and catalase (but not by either enzyme alone). These findings suggest a contribution by OH., one generated by the metal-catalyzed interaction of superoxide and hydrogen peroxide (HaberWeiss reaction) in the anti-Legionella activity of AM.

The ability of penicillins and chloramphenicol to enter human polymorphonuclear leukocytes (PMNLs) and their antibacterial activity against intracellular Haemophilus influenzae type b were studied. Penicillin was excluded whereas chloramphenicol was concentrated in PMNLs; chloramphenicol uptake was not dependent on PMNL energy and was not competitively inhibited by unlabeled drug. PMNLs that had phagocytized opsonized H. influenzae type b were examined after incubation for 24 hr. In the absences of antibiotics, intact intracellular H. influenzae type b organisms were observed in PMNLs by electron microscopy. These PMNLs contained 10(4.5) colony-forming units (cfu) of H. influenzae type b. Addition of penicillin or ampicillin at four, 20, or 40 times the minimal bactericidal concentration (MBC) decreased this density from 10(4.5) to 10(3.5) cfu. In contrast, addition of chloramphenicol at four times the MBC reduced the density to approximately 100 cfu; at 10 times the MBC it reduced the density to approximately 10 cfu. Thus, lipid-soluble antibiotics such as chloramphenicol are concentrated and are bioactive within PMNLs. Such antibiotics may have a significant advantage at the cellular level.

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