IMMUNE DEVIATION FOLLOWING PULSE CYCLOPHOSPHAMIDE METHYLPREDNISOLONE TREATMENT OF MULTIPLE-SCLEROSIS - INCREASED INTERLEUKIN-4 PRODUCTION AND ASSOCIATED EOSINOPHILIA/

Multiple sclerosis (MS) is postulated to be a Th1-type cell-mediated a utoimmune disease. Thus therapies that decrease T cell interferon (IFN )-gamma production or increase interleukin (IL)-4 production would be expected to have an ameliorating effect on MS. Some progressive MS pat ients receiving pulse cyclophosphamide therapy developed peripheral bl ood eosinophilia. We investigated whether cyclophosphamide-treated pat ients had immune deviation toward Th2 responses. We measured cytokine production in patients receiving either monthly intravenous methylpred nisolone (MP), intravenous cyclophosphamide plus methylprednisolone (( CY/MP), methotrexate, IFN-beta 1b, in untreated MS patients, and in he althy controls. Minimal IL-4 was secreted in untreated patients (129 /- 62 pg/ml), methotrexate-treated patients (99 +/- 79 pg/ml), and hea lthy controls (50 +/- 13 pg/ml). A marked increase in IL-4 was observe d in CY/MP patients (1,503 +/- 291 pg/ml). Patients treated with MP (4 18 +/- 160 pg/ml) or IFN-beta 1b (425 +/- 167 pg/ml) showed small incr eases. Eosinophilia in CY/MP-treated patients (6.0 +/- 0.7%) correlate d with increased IL-4. IL-10 production was also increased in CY/MP-tr eated patients. Both CY/MP- and MP-treated groups had decreased produc tion of IFN-gamma compared with untreated MS. These findings demonstra te pronounced immune deviation favoring Th2-type responses after pulse cyclophosphamide therapy.