Murine hypersensitivity pneumonitis: interleukin-4 administration partially abrogates the disease process

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Abstract

C57BL-6 inbred mice were given intranasal instillations of Faeni rectivirgula (150 μg/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 10000 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 103 U IL-4 and 1.31 in mice given antigen and 104 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 sx 105 cells in saline-instilled mice; 8.3 × 105 cells in mice given 103 U IL-4 and F. rectivirgula; 3.2 × 105 cells in mice given antigen and 104 U IL-4; 1.8 × 106 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 μg of hydroxyproline/lung in challenged mice; 170 μg/lung in challenged mice given 103 U IL-4; 131 μg/lung in mice given antigen and 104 U IL-4 and c. 100 μg/lung in control animals). Infusion of 102 U IL-4 weekly had no statistical effect on any marker of inflammation. Blocking of IL-4 activity with 11B11 hybridoma supernatant blocked the anti-inflammatory effect of IL-4. Bronchoalveolar macrophages from mice given F. rectivirgula and excipient, released substantial amounts of tumour necrosis factor alpha (TNFα) upon lipopolysaccharide (LPS) stimulation, and the release of TNFα was significantly reduced by IL-4 treatment. Overall, these results suggest that IL-4 may have anti-inflammatory properties which may have therapeutic values in the treatment of lung inflammatory diseases.

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Supported in part by the Association Pulmonaire du Québec and NSERC CANADA.

1

Michel Denis is a Scholar from the Fonds de la Recherche en Santé du Québec.

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