Differential Transcription of SOCS5 and SOCS7 in Multiple Sclerosis Patients Treated with Interferon Beta or Glatiramer Acetate

Abstract

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-β 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-β (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-β (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.

Keywords

• multiple sclerosis
• jak-stat
• socs5
• socs7
• ifn-<i>β</i>
• glatiramer acetate