Interferon alpha treatment of relapsing–remitting multiple sclerosis: long-term study of the correlations between clinical and magnetic resonance imaging results and effects on the immune function

Abstract

Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-α counteracts many of the proinflammatory actions of IFN-γ and TNF-α. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-α-2a (rIFN-α) (n =12) or placebo (n=8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rlFN-α-treated and in 7/8 placebo-treated patients (P<0.005). Only one new MRI lesion was detected in the rIFN-a group, while 27 new or enlarging lesions were detected in placebo group (P<0.0/J. Baseline lymphocyte IFN-γ (I9.I0±7.I2 U ml^-1) and TNF-α (I8.05±5.34 pg ml^-1) production significantly decreased to 3.03±0.66 (P<0.04) (for IFN-γ) and to 5.78±0.90 (P<0.04) (for TNF-α) after rIFN-α treatment. IFN-γ and TNF-α production was unchanged in the placebo group. rIFN-α was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-α might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.