Interleukin-4 enhances pulmonary clearance of Pseudomonas aeruginosa.
To determine the effects of interleukin-4 (IL-4) on bacterial clearance 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 Pseudomonas aeruginosa. Survival of CCSP-IL-4 mice following bacterial administration was markedly improved compared with that of control mice. While 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 neutrophilic pulmonary infiltration, and this response was similar in the presence or absence of IL-4. Local administration or expression of IL-4 in the mouse lung enhanced pulmonary clearance of P. aeruginosa in vivo and decreased mortality following infection.
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
S
S
Jain-Vora
A M
AM
LeVine
Z
Z
Chroneos
G F
GF
Ross
W M
WM
Hull
J A
JA
Whitsett
D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology; D011510:Proteolipids / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006023:Glycoproteins; D007375:Interleukin-1; D011510:Proteolipids; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4