Human chorionic gonadotropin regulates cytokine production by lympho-cytes from patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that primarily affects young adults, predominantly fe-males. This was partially attributed to sex differences in immunity, which are influenced by changes in sex hormones occurring during women‘s life, among other factors. Furthermore, MS patients experience significant improvement in their symptoms during pregnancy when levels of female sex-hormones signifi-cantly increase. This phenomenon was attributed to immune adaptations oc-curring during gestation which are regulated by paternal antigens and sex hormones.The human chorionic gonadotropin (hCG) was shown to have strong immuno-suppressive abilities. We aimed to analyze here the capacity of the hCG to regulate pro- and anti-inflammatory cytokine production by PBMC from MS pa-tients.Peripheral blood mononuclear cells (PBMC) isolated from 20 MS patients re-ceiving IFNβ1a treatment were cultured with or without recombinant or urinary hCG. Cytokine production in the supernatants was assessed using a CBA ar-ray and cytokine production by lymphocytes and expression of co-stimulatory molecules in B-lymphocytes were evaluated by flow cytometry.hCG reduced the production of TNF by PBMC from MS patients while lowering the percentages of TNF producing T cells and diminishing the production of TNF by B cells. hCG significantly boosted the production of IL-10 by regulatory T cells and CD19high B cells from MS patients. Furthermore, hCG treatment lowered the percentages of CD80+CD86+ expressing B cells within PBMC from MS patients.Overall, our results described a novel and not yet explored mechanisms of ac-tion of hCG in the context of MS.