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

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

ZAFFARONI, MAURO;MARINO, FRANCA;BOMBELLI, RAFFAELLA MARIA;RASINI, EMANUELA;FERRARI, MARCO;LECCHINI, SERGIO;COSENTINO, MARCO
2008

Abstract

Objective: To investigate the endogenous dopaminergic/adrenergic system of lymphocytes in multiple sclerosis (MS) patients during treatment with interferon (IFN)-beta. Methods: Patients with relapsing-remitting MS undergoing IFN-beta 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 rnRNA expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of CA), beta(2)-adrenoceptors (AR) and D2, D3 and D5 dopaminergic receptors (DR). Results: In cells from patients treated with IFN-beta for 12 months the production of CA hugely increased and was less sensitive to IFN-gamma-induced inhibition. Expression of mRNA for TH, beta(2)-AR and DRD5 was already enhanced after I month and further increased up to 6-12 months of treatment. On the contrary, DRD2 mRNA progressively decreased and DRD3 rnRNA did not significantly change over the whole Study period. Conclusions: In MS patients IFN-beta treatment enhances the ability of lymphocytes to produce CA, and induces extensive modifications of both beta(2)-AR and DR-operated pathways. The clinical relevance of these effects deserves consideration.
Multiple sclerosis, Interferon beta, Lymphocytes, Catecholamines, Catecholamine receptors
Zaffaroni, Mauro; Marino, Franca; Bombelli, RAFFAELLA MARIA; Rasini, Emanuela; M., Monti; Ferrari, Marco; A., Ghezzi; G., Comi; Lecchini, Sergio; Cosentino, Marco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/1707779
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