TUMOR-NECROSIS-FACTOR-ALPHA PLUS INTERLEUKIN-1-BETA TREATMENT PROTECTS GRANULOCYTOPENIC MICE FROM PSEUDOMONAS-AERUGINOSA LUNG INFECTION - ROLE OF AN UNUSUAL INFLAMMATORY RESPONSE

We have recently demonstrated that treatment with interleukin 1 beta ( IL-1 beta) plus tumor necrosis factor alpha (TNF alpha) protects granu locytopenic hosts from Pseudomonas aeruginosa aerosol challenge. In th is study we characterized the inflammatory response induced by P. aeru ginosa in granulocytopenic mice treated with 2,000 U IL-1 beta plus 2, 000 U TNF alpha. Treatment with the nonsteroidal anti-inflammatory age nt piroxicam abolished both the protective effect of cytokine treatmen t and the increase in myeloperoxidase (MPO) pulmonary activity. Histop athological studies revealed that, after aerosol challenge with P. aer uginosa, treatment with these cytokines induced migration and extravas ation of mononuclear cells of immature appearance into the lung parenc hyma. These cells contained MPO in their cytoplasm and displayed phago cytic capacity. Resident alveolar macrophages exhibited signs of activ ation and appeared in reduced numbers in bronchoalveolar lavage fluid. We suggest that the inflammatory response promoted by low TNF alpha p lus IL-1 beta doses may be one mechanism responsible for protection of granulocytopenic hosts from P. aeruginosa aerosol challenge.