Difference in effect of single immunosuppressive agents (cyclophosphamide, CCNU, 5-FU) on peripheral blood immune cell parameters and central nervous system immunoglobulin synthesis rate in patients with multiple sclerosis.
Cyclophosphamide (CY), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-fluorouracil (5-FU) were given in single course schedules to chronic progressive multiple sclerosis (MS) patients clinically stable for 6 months. The following peripheral immune cellular parameters were measured before, during and after each drug administration: white blood count (WBC), polymorphonuclear count (PMN), lymphocyte count, percentage of T cells, T cell response to phytohaemagglutinin (PHA), percentage of B cells, percentage of cells bearing receptors for the Fc portion of immunoglobulin (% FcR cells), killer (K) cell activity defined by antibody-dependent cellular cytotoxicity (ADCC), and natural killer (NK) cell activity. Central nervous system (CNS) immunoglobulin G (IgG) synthesis was also measured. The patients were followed carefully by both quantitative and qualitative methods for any change in their neurologic condition. Selective reduction in NK activity was observed with CY and 5-FU while no significant alteration was seen in %FcR cells and K activity. CY differed from 5-FU in reducing lymphocyte count and B cell percentage while 5-FU decreased the percentage of T cells. CCNU, but not the other drugs, reduced T cell proliferative response to PHA. In addition, CCNU, which is known to penetrate well into the nervous system, caused a modest reduction in CNS IgG synthesis, while 5-FU had an uncertain effect. Clinically the patients were unchanged or continued to progress in their disability. The results suggest an independence of the CNS immune from the systemic immune system in MS in response to many immunosuppressive drugs.
D000328:Adult; D003520:Cyclophosphamide / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D007694:Killer Cells, Natural / Q000187:drug effects; D007958:Leukocyte Count; D008130:Lomustine / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011961:Receptors, Fc / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D007074:Immunoglobulin G; D009607:Nitrosourea Compounds; D011961:Receptors, Fc; D008130:Lomustine; D003520:Cyclophosphamide; D005472:Fluorouracil