INTERLEUKIN-4 ENHANCES PULMONARY CLEARANCE OF PSEUDOMONAS-AERUGINOSA

To determine the effects of interleukin-4 (IL-4) on bacterial clearanc e from the mouse lung, transgenic mice expressing IL-4 in respiratory epithelial cells under the control of the Clara cell secretory protein promoter (CCSP-IL-4 mice) were infected intratracheally with Pseudomo nas aeruginosa. Survival of CCSP-IL-4 mice following bacterial adminis tration was markedly improved compared with that of control mice. Whil e bacteria proliferated in lungs of wild-type mice, a rapid reduction in the number of bacteria was observed in the IL-4 mice as early as 6 h postinfection. Similarly, intranasal administration of IL-4 enhanced bacterial clearance from the lungs of wild-type mice. While acute and chronic IL-4 increased the numbers of neutrophils in bronchoalveolar lavage fluid, bacterial infection was associated with acute neutrophil ic pulmonary infiltration, and this response was similar in the presen ce or absence of IL-4. Local administration or expression of IL-4 in t he mouse lung enhanced pulmonary clearance of P. aeruginosa in vivo an d decreased mortality following infection.