PEPITEM regulates the synovial microenvironment during immune-mediated inflammatory arthritis to limit disease

Building on these observations, treatment with PEPITEM in three distinct inflammatory arthritis animal models significantly reduced arthritis severity, joint swelling, leukocyte infiltration and expression of several pro-inflammatory mediators (e.g., JE (CCL2), RANTES, IL-16) in the synovium. Mechanistically, PEPITEM treatment suppressed the COX2 and NF-B signalling pathways. Moreover, PEPITEM altered the composition of leukocyte subsets recruited into the joint.

Conclusion: Collectively, these findings underscore the importance of understanding the dysregulation of the adiponectin-PEPITEM pathway in different immune-mediated inflammatory diseases (IMIDs), such as RA and PsA. The observed differences in expression and downstream signalling through ADIPOR suggest potential targets for therapeutic intervention to restore the balance of this regulatory pathway to mitigate chronic inflammation and disease progression in these patients, paving the way for its clinical use as an alternative and/or combination therapy for early IMIDs.