Impact of immunomodulatory treatment on leukocyte cytokine production in multiple sclerosis patients and healthy donors.
OBJECTIVE
Treatment with interferon(IFN) beta, glatiramer acetate (GLAT) and intravenous immunoglobulins (IVIG) alters the cytokine production in multiple sclerosis (MS) patients. To date, it is not clear whether the effect on cytokines varies among these drugs. Therefore, we analyzed the effects of these drugs on the cytokine profiles of MS patients as well as healthy controls.


METHODS
The in vitro effects of IFNbeta, GLAT and IVIG on leukocyte subsets producing the p40 subunit of interleukin 12 (IL12p40), IFNgamma, tumor necrosis factor (TNF) and interleukin (IL) 10 were assessed in 21 MS patients and 11 healthy volunteers using flow cytometry.


RESULTS
In peripheral vein blood of healthy volunteers, IVIG reduced IL12p40-producing monocytes (p = 0.003) and IFNgamma in CD4+ lymphocytes (p = 0.003). IFNbeta treatment increased the proportion of IFNgamma-producing CD4+ lymphocytes (p = 0.003) whereas GLAT reduced TNF production (p = 0.012). In MS patients, IVIG induced a suppression of leukocytes producing IL12p40 (p < 0.001) and IFNgamma (p = 0.001). IFNbeta decreased monocytes producing IL12p40 (p < 0.001) and increased IL10 (p = 0.005). GLAT reduced IL12p40 (p < 0.001), IFNgamma (p = 0.001 in CD4+ and CD8+ lymphocytes) and TNF production of leukocytes (p < 0.001). In addition, the baseline cytokine patterns were inherently different between individual MS patients.


CONCLUSIONS
IFNbeta, GLAT and IVIG had different effects on cytokine patterns, which might point towards different mechanisms of action. Since the baseline cytokine patterns differed among MS patients, the evaluation of the cytokine pattern might serve as a surrogate marker before starting immunomodulatory treatments and might be helpful to tailor MS therapy effectively to the needs of each individual patient.
Reske
Dirk
D
Department of Neurology, University of Cologne, Cologne, Germany. dirk.reske@uk-koeln.de
Thomas
Anne V
AV
Petereit
Hela-Felicitas
HF
Fink
Gereon R
GR
Schroeter
Michael
M
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D007371:Interferon-gamma