Methotrexate appears to be an effective alternative to
corticosteroid therapy for some patients with
sarcoidosis. The mechanism of action of
methotrexate as an immunosuppressive is unknown. Patients with symptomatic
pulmonary sarcoidosis underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage. Patients were treated with 10 mg
methotrexate or
prednisone weekly for at least 6 months and repeat studies were performed. A comparison was made between those patients receiving
methotrexate (12 patients) and those receiving
prednisone (12 patients). For both groups, there was a significant improvement in the vital capacity with
therapy (
Prednisone: Pre = 2.5 +/- 0.14 L (Mean +/- SEM); Post = 3.1 +/- 0.18 L, p less than 0.01;
Methotrexate: Pre = 2.4 +/- 0.14 L; Post = 2.8 +/- 0.18 L, p less than 0.01). In addition, the percentage of lymphocytes in the lavage fell significantly for both the
prednisone (Pre: 30 +/- 3.5%; Post: 16 +/- 2.7%, p less than 0.001) and
methotrexate (Pre: 37 +/- 3.4%; Post: 13 +/- 2.9%, p less than 0.001) groups. Alveolar macrophages from the symptomatic sarcoid patients were found to be spontaneously releasing
hydrogen peroxide and
tumor necrosis factor.
After treatment with either
prednisone or
methotrexate, alveolar macrophages retrieved by lavage spontaneously released less of either macrophage product. We found that effective doses of
methotrexate for
sarcoidosis led to significant changes in lymphocyte and macrophages retrieved by lavage.