Dynamics of immune cell trafficking in interferon-beta treated multiple sclerosis patients.
OBJECTIVE
To investigate the effects of interferon-beta-1a (IFN-beta-1a) on the trafficking of cell populations in peripheral blood cells of multiple sclerosis (MS) patients.


METHODS
In this open-label pharmacodynamic study, peripheral blood was obtained from 10 relapsing-remitting (RR) MS patients just prior to and at 1, 2, 4, 8, 24, 48, 120, and 168 h after intramuscular injection of 30-microg IFN-beta-1a. Timed samples were also obtained from five controls at 0, 8, 24, 48 and 168 h. The blood cells were analyzed using four-color flow cytometry with antibody conjugates directed against cell surface proteins specific for T cells, B cells, NK cells, and the activation marker, CD69.


RESULTS
IFN-beta-1a treatment resulted in selective, time-dependent effects on many cell populations in peripheral blood. The trafficking of T-helper and T-suppressor/cytotoxic subsets of T cells were qualitatively different. The most prominent effects were on the trafficking of natural killer cells, the levels of which decreased to 23.5% of pretreatment values at 8 h after treatment. The levels of CD69-positive NK cells increased to a peak value of 606% of pretreatment levels at the 24-h time point. In untreated controls, these characteristic trafficking effects were not observed. There was inter-patient heterogeneity in the levels of activated NK cells at the 6-month time point that may potentially be relevant for individualizing IFN-beta therapy.


CONCLUSIONS
IFN-beta treatment can induce specific, selective, and time-dependent trafficking of cells and its effects on different subsets of a given cell type are not qualitatively similar. The dynamics indicate that the activation of NK cells by IFN-beta is possibly dependent on the trafficking of NK cells. The activated NK cell levels after prolonged therapy may potentially provide a surrogate marker for IFN-beta exposure.
Hartrich
Laura
L
Department of Pathology, State University of New York at Buffalo, Buffalo, NY 14260-1200, USA.
Weinstock-Guttman
Bianca
B
Hall
Dennis
D
Badgett
Darlene
D
Baier
Monika
M
Patrick
Kara
K
Feichter
Joan
J
Hong
Jianming
J
Ramanathan
Murali
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D016899:Interferon-beta