PASSIVE IMMUNIZATION AGAINST TUMOR NECROSIS FACTOR AND INTERLEUKIN1 FAILS TO REDUCE LUNG NEUTROPHIL SEQUESTRATION IN CHRONIC SEPSIS

The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) are produced within the lung during sepsis, and may induce neutrophil sequestration resulting in neutrophil-mediated lung injury. We hypothesized that, if there is a cause and effect between TNFμ or IL-1 production and lung neutrophil sequestration during chronic sepsis, TNFμ mRNA and IL-1 mRNA levels in the lung after cecal ligation and puncture should correlate with the number of sequestered neutrophils as measured by the myeloperoxidase (MPO) content of the lung. To test this hypothesis, Swiss Webster mice were subjected to varying degrees of infectious challenge by single and double-puncture cecal ligation and puncture, or simultaneous antibiotic treatment, and their lungs and blood were harvested at 24 h. Lung TNFμ and IL-1 μ mRNAs were measured by the reverse-transcription differential polymerase chain reaction, and MPO was measured by colorimetric assay. TNFa serum levels showed no correlation with the MPO content of the lung, whereas IL-1 levels were undetectable. Lung TNFa mRNA correlated weakly, and IL-1 /3 mRNA exhibited a strong correlation with lung MPO (r = .9, p < .01), but administration of anti-TNFμ- or anti-IL-1 -neutralizing antibodies did not prevent a rise in lung MPO. IL-1μ mRNA in bronchoalveolar macrophages correlated well with whole lung tissue IL-1μ mRNA levels (r = .91, p < .01). These results suggest that IL-1μ mRNA levels in lung tissue or bronchoalveolar macrophages may predict lung neutrophil sequestration in sepsis, but the precise involvement of IL-1 in the process is unclear.