The effect of high dosage of methotrexate, associated with folinic acid, on the suppression of tuberculin sensitivity in guinea-pigs.

Methotrexate administered over a period of 8 weeks reduced tuberculin skin sensitivity in guinea-pigs, the effect waning in the later part of the period. The delayed administration of folinic acid successfully reduced the toxicity of methotrexate so that the dose of the latter could be increased three-fold; there was then no impairment, and probably some increase, of its inhibition of tuberculin sensitivity. However, the suppression was not complete even with these large doses of the drug. In the spleen at the termination of an experiment, there was a striking diminution in the number of small lymphocytes in animals given methotrexate with or without folinic acid, compared with untreated animals. Animals given methotrexate plus folinic acid showed much larger spleens than did untreated animals, the spleen of the single survivor of the group on methotrexate alone being intermediate in size. There was a haemopoietic reaction corresponding in degree to the size of the spleen in the three groups.