S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R/B220 Cells in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic illness characterised by progressive central nervous system (CNS) degeneration. The efficacy of most current MS medicines is limited, and significant adverse effects remain a concern. STAT3 inhibitors show potential for treating several immunological diseases. The current study demonstrates that S3I-201, a well-established STAT3 inhibitor, effectively treats PLP139−151-induced EAE in SJL/J mice. After establishing EAE, mice were administered S3I-201 intraperitoneally (10 mg/kg) daily from day 14 through day 35. Flow cytometry was used to measure the effect of S3I-201 on the expression levels of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 in CD19+ and CD45R/B220+ B cells. RT-PCR was also used to study the effect of S3I-201 on the mRNA expression levels of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 in brain tissue. S3I-201 administration reduced the number of CD19+IL-6+, CD45R+IL-6+, CD19+iNOS+, CD45R+iNOS+, CD19+Notch1+, CD45R+Notch3+, CD19+GM-CSF+, CD45R+GM-CSF+, CD19+NF-κB p65+, and CD45R+NF-κB p65+ cells in EAE mice. Furthermore, S3I-201 administration reduced the expression of IL-6, iNOS, Notch1, Notch3, GM-CSF, and NF-κB p65 mRNA in brain tissue. S3I-201 inhibits the signalling of inflammatory mediators via various cellular pathways. Our findings suggest that S3I-201 may have therapeutic effects on EAE and may slow its progression in MS.