Interferon gamma, IL2, IL4, IL10 and TNFalpha secretions in multiple sclerosis patients treated with an anti-CD4 monoclonal antibody.
In order to better understand the mechanisms of action of a monoclonal anti-CD4/BF5 antibody(mAb), cytokine secretions were studied in 14 multiple sclerosis (MS) patients treated in a phase 1 trial. Secretion patterns of IFNgamma, IL2, IL4, IL10 and TNFalpha by peripheral blood mononuclear cells were studied before (DO) and after (D30) the treatment. We decided to undertake this study because in a previous one we observed no variations in serum levels of TNFalpha, IFNgamma, IL1, IL6. Results showed significant reductions in IFNgamma, IL2 and TNFalpha secretions after treatment. The anti-CD4 mAb seemed to act on both Th1- and Th2-cells but with preferential action on Th1-cells. Results on Th2-cells were less obvious even though a significant decrease in IL10 was observed. There was no correlation between any of the immunological markers studied and disease activity. This study demonstrates that pharmacological modifications of the CD4 receptor can induce variations in several cytokine secretion levels. It also stresses the role played by Th1- and Th2-cells in the etiopathogenesis of MS.
Lopez
E
E
Etablissement de Transfusion Sanguine, Besançon, France.
Racadot
E
E
Bataillard
M
M
Berger
E
E
Rumbach
L
L
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4