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

ObjectiveTo investigate the endogenous dopaminergic/adrenergic system of lymphocytes in multiple sclerosis (MS) patients during treatment with interferon (IFN)-β.MethodsPatients 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), β2-adrenoceptors (AR) and D2, D3 and D5 dopaminergic receptors (DR).ResultsIn 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, β2-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.ConclusionsIn MS patients IFN-β treatment enhances the ability of lymphocytes to produce CA, and induces extensive modifications of both β2-AR and DR-operated pathways. The clinical relevance of these effects deserves consideration.