Involvement of Cytokines in the Pathogenesis of Hypersensitivity Pneumonitis: Evaluation of Immunotherapeutic Measures in a Mouse Model

C57BL/6 inbred strain mice were instilled intranasally with150 μg/day of the actinomycete Faeni rectivirgula three days a week as a model of farmer's lung disease.Instilled mice developed a strong alveolitis manifested by a large increase in the number of cells in thebronchoalveolar lavage (BAL) (4.1 x 104 cells in saline controls versus 5.28x 105 cells in F rectivirgula-instilledmice). This influx was associated with a substantial release of pro-inflanm1atory cytokine in the BAL; 170U/mL of interleukin (IL)-1 in instilled mice whereas saline instilled mice had undetectable levels of cytokinesin the BAL. In addition, pulmonary fibrosis was evident in challenged mice at three weeks (twofold increasein lung hydroxyproline levels). Infusion of a rabbit antimouse tumour necrosis factor-alpha was associatedwith an almost complete abrogation of all markers of the disease. Also, administration of cyclosporine A(50 mg/kg/day) partially prevented the alveolitis (P<0.01) and totally prevented cytokine release and lungfibrosis in challenged mice. These findings underscore the tmmunological basis of hypersensitivitypneumonitis, and suggest that antagonism of inflammatory cytokines may hold promise in the treatmentof this pathology