TY - JOUR
T1 - Therapy with interferon-β modulates endogenous catecholamines in lymphocytes of patients with multiple sclerosis
AU - Zaffaroni, Mauro
AU - Marino, Franca
AU - Bombelli, Raffaella
AU - Rasini, Emanuela
AU - Monti, Marta
AU - Ferrari, Marco
AU - Ghezzi, Angelo
AU - Comi, Giancarlo
AU - Lecchini, Sergio
AU - Cosentino, Marco
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - Catecholamine receptors
KW - Catecholamines
KW - Interferon beta
KW - Lymphocytes
KW - Multiple sclerosis
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U2 - 10.1016/j.expneurol.2008.08.015
DO - 10.1016/j.expneurol.2008.08.015
M3 - Article
C2 - 18824168
AN - SCOPUS:56349094317
VL - 214
SP - 315
EP - 321
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -