Therapy with interferon-β modulates endogenous catecholamines in lymphocytes of patients with multiple sclerosis

Objective: To investigate the endogenous dopaminergic/adrenergic system of lymphocytes in multiple sclerosis (MS) patients during treatment with interferon (IFN)-β. Methods: Patients with relapsing-remitting MS undergoing IFN-β treatment were prospectively studied during the first year of treatment. Circulating lymphocytes were obtained at baseline and after 1, 3, 6 and 12 months of treatment and assayed for catecholamine (CA) production and mRNA expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of CA), β ₂-adrenoceptors (AR) and D2, D3 and D5 dopaminergic receptors (DR). Results: In cells from patients treated with IFN-β for 12 months the production of CA hugely increased and was less sensitive to IFN-γ-induced inhibition. Expression of mRNA for TH, β ₂-AR and DRD5 was already enhanced after 1 month and further increased up to 6-12 months of treatment. On the contrary, DRD2 mRNA progressively decreased and DRD3 mRNA did not significantly change over the whole study period. Conclusions: In MS patients IFN-β treatment enhances the ability of lymphocytes to produce CA, and induces extensive modifications of both β ₂-AR and DR-operated pathways. The clinical relevance of these effects deserves consideration.