THE EFFECT OF TREATMENT WITH INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR ON PSEUDOMONAS-AERUGINOSA LUNG INFECTION IN A GRANULOCYTOPENIC MOUSE MODEL

The efficacy of treatment with interleukin-1 beta (IL-1 beta) and tumo r necrosis factor-alpha (TNF alpha) on Pseudomonas aeruginosa pneumoni a was evaluated in a granulocytopenic mouse model. Combined intravenou s administration of 2000 U IL-1 beta plus 2000 U TNF alpha significant ly diminished mortality from aerosol challenge with P. aeruginosa. Mic e treated with IL-1 beta, TNF alpha, or both also exhibited a signific ant enhancement in pulmonary clearance of P. aeruginosa. Combined cyto kine administration induced an increase in the pulmonary content of my eloperoxidase activity. Mature leukocytes were not detected in either circulation or bronchoalveolar lavage fluid from granulocytopenic, cyt okine-treated mice. In conclusion, IL-1 beta and TNF alpha treatment e xhibited a synergistic protective effect from pulmonary P. aeruginosa challenge in granulocytopenic hosts, probably due to enhancement of no nspecific antibacterial mechanisms. (C) 1994 Academic Press, Inc.