Therapy with interferon-beta 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)-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 mRNA 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 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-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.
Zaffaroni
Mauro
M
Multiple Sclerosis Center, Hospital S. Antonio Abate, Gallarate, VA, Italy.
Marino
Franca
F
Bombelli
Raffaella
R
Rasini
Emanuela
E
Monti
Marta
M
Ferrari
Marco
M
Ghezzi
Angelo
A
Comi
Giancarlo
G
Lecchini
Sergio
S
Cosentino
Marco
M
D000328:Adult; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D050641:Receptors, Dopamine D5 / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D055815:Young Adult
D002395:Catecholamines; D007155:Immunologic Factors; D018343:Receptors, Adrenergic, beta-2; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050641:Receptors, Dopamine D5; D016899:Interferon-beta; D014446:Tyrosine 3-Monooxygenase