Murine hypersensitivity pneumonitis: interleukin-4 administration partially abrogates the disease process.
C57BL-6 inbred mice were given intranasal instillations of Faeni rectivirgula (150 micrograms/day, 3 days a week for 3 weeks) to produce a lung inflammatory reaction which mimics Farmers' lung in humans. Challenged mice developed a strong inflammatory response in their lungs, based on various markers (lung index, bronchoalveolar cell number, fibrosis). The effect of interleukin-4 (IL-4) was studied by infusing mice intraperitoneally with 100, 1000 or 10,000 units of IL-4 weekly during the challenge period. It was shown that IL-4 infusion decreased the inflammatory response, as seen by a decreased lung index (1.7 in mice given F. rectivirgula and 10(3) U IL-4 and 1.31 in mice given antigen and 10(4) U IL-4 weekly versus 2.3 in mice instilled with F. rectivirgula). Interleukin-4 infusion also partially abrogated the F. rectivirgula-induced alveolitis, as seen by a decrease in cell numbers in the broncho-alveolar lavage (BAL) (1.3 x 10(5) cells in saline-instilled mice; 8.3 x 10(5) cells in mice given 10(3) U IL-4 and F. rectivirgula; 3.2 x 10(5) cells in mice given antigen and 10(4) U IL-4; 1.8 x 10(6) cells in mice given F. rectivirgula only). Also, it was apparent that IL-4 administration could partially block the appearance of the fibrosis induced by F. rectivirgula (220 micrograms of hydroxyproline/lung in challenged mice; 170 micrograms/lung in challenged mice given 10(3) U IL-4; 131 micrograms/lung in mice given antigen and 10(4) U IL-4 and c. 100 micrograms/lung in control animals). Infusion of 10(2) U IL-4 weekly had no statistical effect on any marker of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ghadirian
E
E
Montreal General Hospital Research Institute, Quebec, Canada.
Denis
M
M
D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D015847:Interleukin-4 / Q000627:therapeutic use*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4