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Murine hypersensitivity pneumonitis: interleukin-4 administration partially abrogates the disease process
1Montreal General Hospital Research Institute, Quebec, Canada.
Abstract:
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)
Insights
Interleukin-4 (IL-4) treatment in mice reduced lung inflammation and fibrosis caused by Faeni rectivirgula, a model for Farmers' lung. Higher IL-4 doses showed a greater protective effect against this lung inflammatory reaction.
Area of Science:
- Immunology
- Pulmonary Medicine
- Toxicology
Background:
- Farmers' lung is a hypersensitivity pneumonitis caused by inhaling moldy hay dust.
- Animal models are crucial for understanding the pathogenesis and developing treatments for lung inflammatory diseases.
Purpose of the Study:
- To investigate the therapeutic potential of interleukin-4 (IL-4) in a mouse model of Farmers' lung.
- To evaluate the effect of IL-4 on lung inflammation, alveolitis, and fibrosis induced by Faeni rectivirgula.
Main Methods:
- C57BL-6 mice were intranasally instilled with Faeni rectivirgula to induce lung inflammation.
- Mice received weekly intraperitoneal infusions of varying doses of IL-4 (100, 1000, or 10,000 units) during the challenge period.
- Lung inflammation was assessed using lung index, bronchoalveolar lavage (BAL) cell counts, and hydroxyproline levels for fibrosis.
Main Results:
- IL-4 infusion significantly decreased the lung index, indicating reduced lung inflammation.
- Higher doses of IL-4 (1000 and 10,000 units) partially abrogated F. rectivirgula-induced alveolitis, evidenced by lower BAL cell counts.
- IL-4 administration also partially blocked the development of lung fibrosis, as shown by reduced hydroxyproline content.
Conclusions:
- Interleukin-4 demonstrates a dose-dependent protective effect against F. rectivirgula-induced lung inflammation and fibrosis in mice.
- IL-4 may represent a potential therapeutic agent for managing Farmers' lung and similar inflammatory lung conditions.
