Protective effects of histamine H4 receptor antagonist on the inflammatory responses in B cells in a mouse model of multiple sclerosis.

BACKGROUND

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) driven by autoimmune mechanisms. However, growing evidence indicates that B lymphocytes may contribute to the disease through antigen presentation and the production of proinflammatory mediators. This study aimed to examine the effect of JNJ 10191584 (JNJ), a potent and selective H4R antagonist, on EAE progression and to uncover the underlying mechanisms.

METHODS

The research explored the potential impact of H4R antagonists on inflammatory responses in B cells within an EAE mouse model of MS. EAE mice received an oral dose of JNJ at 6 mg/kg daily, starting on day 10 and continuing until day 42. Flow cytometry assessed JNJ's effect on the expression of NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, TNF-α, and MCP-1 in CD19+ B cells. We used RT-PCR to assess the impact of JNJ on mRNA levels of these inflammatory markers in brain tissue.

RESULTS

In EAE mice, JNJ treatment reduced the number of CD19+ cells expressing NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, and MCP-1. Additionally, JNJ decreased mRNA expression of inflammatory markers in brain tissue compared with vehicle-treated mice.

CONCLUSIONS

These results suggest that targeting H4R with antagonists could offer a new therapeutic approach for MS by specifically modulating B-cell-mediated inflammation.