ABSTRACT
I. INTRODUCTION Interferon-0 (IFN-/3) has shown therapeutic effectiveness in decreasing the exacerbation rate and magnetic resonance imaging (MRI) lesions of multiple sclerosis (MS). In one study, 8 million units (MU) IFN-/3-lb was administered subcutaneously every other day to 372 patients (1,2), and in another study, 1 MU natural fibroblast IFN-/3 was administered intrathecally once a week to 69 patients (3). These doses and routes were selected on the basis of pharmacokinetic studies of IFN-/3 and IFN-induced proteins, which defined the dose dependence and duration of the effective biological response to IFN-0 versus the side effects. These biological responses to IFN include increased 2' ,5'-oligoadenylate synthetase (2,5OAS) activity in peripheral blood mononuclear cells (PBMCs), /32-microglobulin and neopterin in serum, and HLA class I and II surface antigens on monocytes. Further consideration of IFN-0 pharmacokinetics and biological response may reveal more effective dose/schedule combinations of IFN-13 for MS, as well as IFN's mechanism of action.
