J Neuroimmunol. 2003 Jun;139(1-2):84-92
Hartrich L, Weinstock-Guttman B, Hall D, Badgett D, Baier M, Patrick
K, Feichter J, Hong J, Ramanathan M.
Department of Pathology, State University of New York at Buffalo, 14260-1200,
Buffalo, NY, USA
PURPOSE:
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-&mgr;g 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.