RESUMO
The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing-remitting phase, treated with IFN-ß or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-ß (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0-160) than in healthy subjects (0 range, 0-106). The same pattern was observed in MS patients treated with IFN-ß (68 pg/mL, range 0-160) compared to patients treated with GA (51 pg/mL, range 0-114), and in MS females (64 pg/mL, range 0-161) compared to healthy females (0, range 0-99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.
Assuntos
Acetato de Glatiramer/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
Multiple sclerosis (MS) is an autoimmune disease characterized by a triad of inflammation, demyelination and gliosis. Because the suppressors of cytokine signaling (Socs) regulate the immune response, we quantified SOCS1 and SOCS3 transcription in peripheral blood leukocytes of patients with MS. SOCS1 transcription decreased significantly in MS patients compared with neurologically healthy persons (0.08±0.02 vs. 1.02±0.23; p=0.0001); while SOCS3 transcription increased in MS patients compared with controls (2.76±0.66 vs. 1.03±0.27; p=0.0008). Our results showed an imbalance of SOCS1 and SOCS3 transcription in MS patients, and a moderated negative correlation between them (Spearman's r=-0.57; p=0.0003).
