PASSIVE-IMMUNIZATION AGAINST TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 FAILS TO REDUCE LUNG NEUTROPHIL SEQUESTRATION IN CHRONIC SEPSIS

The proinflammatory cytokines tumor necrosis factor (TNF) and interleu kin-1 (IL-1) are produced within the lung during sepsis, and may induc e neutrophil sequestration resulting in neutrophil-mediated lung injur y. We hypothesized that, if there is a cause and effect between TNF al pha or IL-1 production and lung neutrophil sequestration during chroni c sepsis, TNF alpha 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 lu ng. To test this hypothesis, Swiss Webster mice were subjected to vary ing degrees of infectious challenge by single and double-puncture ceca l ligation and puncture, or simultaneous antibiotic treatment, and the ir lungs and blood were harvested at 24 h. Lung TNF alpha and IL-1 bet a mRNAs were measured by the reverse-transcription differential polyme rase chain reaction, and MPO was measured by colorimetric assay. TNF a lpha serum levels showed no correlation with the MPO content of the lu ng, whereas IL-1 levels were undetectable. Lung TNF alpha mRNA correla ted weakly, and IL-1 beta mRNA exhibited a strong correlation with lun g MPO (r = .9, p < .01), but administration of anti-TNF alpha- or anti -IL-1-neutralizing antibodies did not prevent a rise in lung MPO, IL-1 beta mRNA in bronchoalveolar macrophages correlated well with whole l ung tissue IL-1 beta mRNA levels (r = .91, p < .01). These results sug gest that IL-1 beta mRNA levels in lung tissue or bronchoalveolar macr ophages may predict lung neutrophil sequestration in sepsis, but the p recise involvement of IL-1 in the process is unclear.