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Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin-4 production and associated eosinophilia

✍ Scribed by Derek R. Smith; Konstantin E. Balashov; David A. Hafler; Samia J. Khoury; Dr. Howard L. Weiner


Book ID
102707839
Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
794 KB
Volume
42
Category
Article
ISSN
0364-5134

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✦ Synopsis


Multiple sclerosis (MS) is postulated to be a Thl-type cell-mediated autoimmune disease. Thus therapies that decrease T cell interferon (1FN)-y production or increase interleukin (1L)-4 production would be expected to have an ameliorating effect on MS. Some progressive MS patients receiving pulse cyclophosphamide therapy developed peripheral blood eosinophilia. We investigated whether cyclophosphamide-treated patients had immune deviation toward Th2 responses. We measured cytokine production in patients receiving either monthly intravenous methylprednisolone (MP), intravenous cyclophosphamide plus methylprednisolone (CY/MP), methotrexate, IFN-P1 b, in untreated MS patients, and in healthy controls. Minimal IL-4 was secreted in untreated patients (129 2 62 pg/ml), methotrexate-treated patients (99 f 79 pg/ml), and healthy controls (50 f 13 pg/ml). A marked increase in IG4 was observed in CY/MP patients (1,503 2 291 pg/ml). Patients treated with MP (418 f 160 pg/ml) or IFN-Plb (425 f 167 pg/ml) showed small increases. Eosinophilia in CY/MP-treated patients (6.0 2 0.7%) correlated with increased IG4. IL-10 production was also increased in CY/MP-treated patients. Both CY/MPand MP-treated groups had decreased production of IFN-y compared with untreated MS. These findings demonstrate pronounced immune deviation favoring Th2-type responses after pulse cyclophosphamide therapy.