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Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia
Author(s) -
Smith Derek R.,
Balashov Konstantin E.,
Hafler David A.,
Khoury Samia J.,
Weiner Howard L.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410420307
Subject(s) - methylprednisolone , cyclophosphamide , methotrexate , medicine , eosinophilia , multiple sclerosis , immune system , gastroenterology , immunology , chemotherapy , endocrinology
Multiple sclerosis (MS) is postulated to be a Th1‐type cell‐mediateds autiommune disease. Thus therapies that decrease T cell interferon (IFN)‐γ production or increase interleukin (IL)‐4 production would be expected to have an ameliorating effect on MS. Some progressive MS patients receiving pulse cyclophosphamide therapy developed periheral 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‐β1b, in untreated MS patients, and in healthy controls. Minimal IL‐4 was secreted in untreated patients (129 · 62 pg/ml), methotrexate‐treated patients (99 · 79 pg/ml), and healthy controls (50 · 13 pg/ml). A marked increase in IL‐4 was observed in CY/MP patients (1,503 · 291 pg/ml). Patients treated with MP (418 · 160 pg/ml) or IFN‐β1b (425 · 167 pg/ml) showed small increases. Eosinophilia in CY/MP‐treated patients (6.0 · 0.7%) correlated with increased IL‐4. IL‐10 production was also increased in CY/MP‐treated patients. Both CY/MP‐ and MP‐treated groups had decreased production of IFN‐γ compared with untreated MS. These findings demonstrate pronounced immune deviation favoring Th2‐type responses after pulse cyclophosphamide therapy.