Chronic systemic high‐dose recombinant interferon alfa‐2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing‐remitting multiple sclerosis

Abstract

We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p< 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.

Regulation of Activated CD4+ T Cells by NK Cells via the Qa-1–NKG2A Inhibitory Pathway

“…Indeed, the ability of IFN-a and IFN-b to ameliorate MS in humans (Willenborg et al, 1996;Jacobs et al, 2000;Steinman and Zamvil, 2006) and of IFN-g to inhibit EAE in mice (Durelli et al, 1995) may reflect the ability of these cytokines to transiently activate NK-dependent regulatory responses (Edwards et al, 1985). However, because IFN treatment also upregulates Qa-1 expression on T cells (Ota et al, Immunity 26, 593-604, May 2007 ª2007 Elsevier Inc. 601 Immunity Qa-1-Dependent Protection of Adaptive Immunity 2005), the short duration and usually modest nature of these therapeutic effects may reflect a Qa-1-dependent decrease in NK activation and associated immunoregulatory activity.…”

Review: cytokines and the pathogenesis of multiple sclerosis

“…Several cytokines have been tested in clinical trials. Among them are IFN-a and IFN-P, which have beneficial effects in MS (Interferon+ Multiple Sclerosis Group, 1993;Durelli et al, 1994). A trial with TGF-P in MS is underway.…”

Long-Lasting Remission of Pulmonary Metastases of Renal Cell Cancer under IFN-b Therapy in a Patient with Multiple Sclerosis

“…Treatment with IL-2 and/or IFN-α, which are well established in RCC, was not initiated after diagnosis of pulmonary metastasis in order to avoid the risk of deterioration of MS, particularly because clinical experience with both cytokines in MS was limited at that time. Nowadays, there are clinical data showing that IFN-α, another type-I interferon, can also be efficient in MS [10,11]. However, the larger number of clinical data and the longer follow-up supports the use of IFN-β in MS.…”