Open Access Research

A gender-related action of IFNbeta-therapy was found in multiple sclerosis

Ida Contasta1, Rocco Totaro2, Patrizia Pellegrini1, Tiziana Del Beato1, Antonio Carolei2 and Anna Maria Berghella1*

Author Affiliations

1 Consiglio Nazionale delle Ricerche (CNR), Istituto di Farmacologia Traslazionale (IFT), via G Carducci, 32-Rotilio Center, L’Aquila 67100, Italy

2 Dipartimento di Neurologia dell’Università di L’Aquila, L’Aquila 67100, Italy

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Journal of Translational Medicine 2012, 10:223  doi:10.1186/1479-5876-10-223

Published: 14 November 2012

Abstract

Background

Understanding how sexual dimorphism affects the physiological and pathological responses of the immune system is of considerable clinical importance and could lead to new approaches in therapy. Sexual dimorphism has already been noted as an important factor in autoimmune diseases: the aim of this study was to establish whether sexual dimorphism in autoimmune diseases is the result of differing pathways being involved in the regulation of T-helper (Th) cell network homeostasis.

Methods

We focused on sexually dimorphic changes in the immune response in multiple sclerosis (MS) patients in order to ascertain how these alterations relate to the pathway regulation of the cytokine homeostasis and the Th cell networks. We studied antigen presenting cell (APC)-dependent T cell activation in groups of healthy subjects, in patients under interferon (IFN) β-therapy and untreated. Cytokines, soluble (s) CD30 and the expanded disability status scale (EDSS) were used as biomarkers for T cell differentiation and neurological deficit.

Results

The data confirm our belief that sexual dimorphism in autoimmune diseases is the result of differing pathways that regulate Th cell network homeostasis: interleukin (IL) 6 pathways in women and IFNγ pathways in men. Given the increased susceptibility of women to MS and the significance of IL6 in the autoimmune process compared to IFNγ, it is logical to assume that IL6 pathways are in some way implicated in the prevalence of autoimmune diseases in women. Indeed, our data indicate that IL6 pathways are also involved in T regulatory (Treg) cell imbalance and an increase in neurological deficit in both men and women groups of MS patients, underlining the autoimmune etiology of multiple sclerosis. In further support of differing cytokine pathways in men and women, we noted that the efficacy of IFNβ-treatment in the re-establishment of Th-network balance and in the delaying of the neurological disability progression is linked to the IL6 pathway in women, but to the IFNγ pathway in men. Lastly, we also identified specific gender biomarkers for the use in therapy.

Conclusions

The identification of gender-specific drugs is of considerable importance in translational medicine and will undoubtedly lead to more appropriate therapeutic strategies and more successful treatment.

Keywords:
Gender differences; Autoimmune diseases; Multiple sclerosis; Th cytokine networks; Th cell networks; CD30; Clinical targets; Clinical biomarkers