Therapeutic effects of pegylated-interferon-α2a in a mouse model of multiple sclerosis

Abstract

Introduction: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model.

Material and methods: EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG_35-55) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis.

Results: Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals.

Conclusions: These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.

Keywords: Peg interferon alpha 2a; antioxidant; experimental autoimmune encephalomyelitis; multiple sclerosis.

Fig. 1

Effect of Peg-IFN α-2a on clinical score of experimental autoimmune encephalomyelitis. Female C57BL/6 mice in the IFN group were administered with 0.1 ml Peg-IFN α-2a from the first day after immunisation for three weeks via subcutaneous injection at an interval of every five days. Disease severity was assessed by a visual cumulative scoring system. Cumulative scores from day 10 until day 21 are given as mean ±SEM; *p < 0.05 is shown for each data point by Mann-Whitney U-test comparing treatment versus control

Fig. 2

Effect of Peg-IFN α-2a on EAE onset. In the IF N group, Peg-IFN α-2a therapy showed a delay at onset of disease compared to control mice; *p < 0.01

Fig. 3

Representative light microscopic view of histopathological slides of central nervous system in different groups. A) H&E staining of brain sections showed that Peg-IFN α-2a therapy could suppress the progression of inflammation significantly by restricting leukocyte infiltration. B) LFB staining showe that Peg-IFN α-2a could decrease the extent of demyelination. N – normal, C – control, I – Peg-IFN α-2a treated

Fig. 4

The effect of Peg-IFN α-2a on serum SOD activity. It was observed that treatment with Peg interferon-2a increased SOD activity compared to control group, but this difference was not statistically significantly (p = 0.351)

Fig. 5

The effect of Peg-IFN α-2a on serum GR activity. It was observed that treatment with Peg interferon-2a increased GR activity compared to the control group but was not statistically significant (p = 0.099). However, the difference between normal group and control group was statistically significantly (p < 0.001)

Fig. 6

The effect of Peg-IFN α-2a on serum TAC. Treatment with Peg-IFN α-2a significantly increased TAC (2.25 ±0.49) compared to the control group (1.68 ±0.22); *p = 0.041

Fig. 7

The effect of Peg-IFN α-2a on serum IL-6 concentration. It was observed that treatment with Peg-IFN α-2a significantly decreased IL-6 concentration compared to the control group (p = 0.046)