Multiple Sclerosis, 1 October 2002, vol. 8, no. 6, pp. 485-491(7)
Dhib-Jalbut S.; Chen M.; Henschel K.; Ford D.; Costello K.; Panitch H.
 Department of Neurology, University of Maryland and the Baltimore VA Medical Centre, Baltimore, Maryland, USA
The combined treatment with interferon b (IFNb) and glatiramer acetate (GA) is of current interest in multiple sclerosis (MS).
The therapeutic effect of GA in MS is believed to be mediated by GA-specific Th2 cells.
IFNb has a significant anti-proliferative effect on GA-induced lymphoproliferation in vitro.
Therefore, we examined the possibility that IFN may interfere with the generation and phenotype of GA T-cell responses in MS patients receiving combined therapy.
Sixty-six GA-specific T-cell lines (TCL) were generated ex vivo from five MS patients enrolled in an open-label clinical trial of combined IFNb/GA treatment.
Controls included 83 pretreatment and 131 on-treatment GA-TCL from 11 MS patients treated with GA only, and five GA-TCL generated from four patients receiving IFNb-1a monotherapy.
IFN g and IL-5 (markers of Th1 and Th2 responses, respectively) were assayed by ELISA in GA-TCL supernatants.
Th1/Th2 bias was defined by the IFN g /IL-5 level ratio ( > 2=Th1 bias, < 0.5=Th2 bias, and 0.5– 2=Th0 bias).
The frequency with which GA-reactive TCL were generated was 37.0% for the patients in the combination trial compared to 33.3% in the patients receiving GA alone.
The mean stimulation index of the GA-TCL was 8.41 (range 2–42) for the combination compared to a mean of 6.29 (range 2–37) for the GA-treated group – a nonsignificant difference.
Mean GA-TCL IFNg production was significantly lower in all treatment groups compared to pretreatment.
IL-5 levels were enhanced in all treatment groups compared to pretreatment levels, but the change was not statistically significant.
The Th1/Th0/Th2 distribution of GA-TCL was 7%/30%/63% for the GA+IFNb group, compared to 48%/21%/31% pre-GA treatment.
All five GA-TCL from the IFNb-1a monotherapy patients were Th2-biased.
We conclude that IFNb-1a does not affect the generation of GA-reactive T cells in vivo.
Although more Th0 GA-TCL occurred with combination therapy than with GA treatment alone, both groups shared an overall Th2 bias.
Therefore, we speculate that combined therapy is unlikely to reduce the efficacy of GA treatment in MS.