EFFECT OF CORTICOSTEROIDS ON HUMAN IMMUNE-RESPONSE - COMPARISON OF ONE AND 3 DAILY 1 GM INTRAVENOUS PULSES OF METHYLPREDNISOLONE

Abstract

In spite of the increasing use of single and multiple pharmacologic i.v. pulses of MPS [methylprednisolone] for immunosuppression in various diseases, their immunosuppressive effects have not been documented. Two groups of 6 patients with classic RA [rheumatoid arthritis] unresponsive to conventional therapy were treated with 1 or 3 daily 1 g i.v. doses of MPS. The immune response and clinical activity over 16 wk was then assayed. Lymphocytopenia with selective T [thymus-derived] lymphocyte suppression was noted 2 h following each infusion, which was maximal at 6 h with complete recovery 24 h after each dose beyond which no lymphocytopenia or T lymphocyte depletion was seen. Preservation of skin test positivity to recall antigens such as PPD [purified protein derivative] and histoplasmin, rise in antibody titers to the secondary antigens tetanus [toxoid] and typhoid, and the primary antibody response to KLH [keyhole limpet hemocyanin] were found in both groups after treatment. Serum .gamma.-globulin concentrations were unchanged. Five of 6 patients receiving 3 doses and 3 of 6 receiving 1 dose had satisfactory improvement in clinical parameters, with maximal benefit seen within the first 4 days. Six patients still felt better at 4 wk, and 1 patient in each group entered a clinical remission greater than 16 wk. Higher and repeated doses of MPS did not cause greater lymphocytopenia or more prolonged suppression of recirculating lymphocytes than the conventional oral doses. The clinical benefits stem from reduction of inflammation. It is doubtful that pulse therapy by itself induces significant generalized immunosuppression.