Time of interferon-beta 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients

During initiation of interferon-beta (IFN-beta) therapy, many multiple sclerosis (MS) patients experience systemic side effects which may depend on the time point of IFN-beta injection. We investigated the time course of plasma hormone-, cytokine- and cytokine-receptor concentrations after the first injection of IFN-beta either at 8.00 a.m. (group A) or at 6.00 p.m. (group B) and quantified clinical side effects within the first 9 h in 16 medication free patients with relapsing-remitting MS. This investigation was repeated after 6-month IFN-beta therapy. Plasma ACTH and cortisol concentrations followed their physiological rhythms, with lower levels in the evening compared to the morning, but raised earlier and stronger in group B after IFN-beta administration. IFN-beta injection in the evening led to a prompter increase of plasma IL-6 concentrations and temperature during the first hours and correlated to more intense clinical side effects compared to group A. Plasma IL-10 concentrations increased more in group A compared to group B, but sTNF-RI and sTNF-RII concentrations raised 7 h after IFN-beta injection only in group B. Acute effects on plasma hormone and cytokine concentrations adapted after 6-month IFN-beta treatment, while diurnal variations were still present. Baseline sTNF-RII concentrations were elevated after 6-month IFN-beta therapy only in group A. Our results show that time point of IFN-beta injection has differential effects on acute changes of plasma hormone and cytokine concentrations and is related to systemic side effects. This may have implications on the tolerability and effectiveness of IFN-beta therapy.