PEPITEM is a circulating peptide involved in resolution of inflammation and reduction of chronic inflammation. Levels of PEPITEM decline with age, which is one of the reasons why inflammatory athritis becomes worse with age, in that this inhibitory mechanism declines in effectiveness. Studies in animal models have shown that injection of synthetic PEPITEM can improve symptoms; an example of this sort of work is noted here.
Inflammatory arthritis is a group of diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA), where the immune system attacks the joints, causing severe joint damage, pain, and disability. Under normal conditions, adiponectin in the bloodstream stimulates white blood cells to produce PEPITEM, which in turn reduces white blood cell migration in the tissues, preventing an unregulated inflammatory response. However, in inflammatory arthritis, white blood cells fail to respond to adiponectin, and secrete less PEPITEM in the joint. The natural 'break' that prevents white cell migration into the joint cavity is lost, and the inflammatory response becomes unregulated.
The initial study of peripheral blood mononuclear cells (PBMCs, white blood cells) harvested from treatment-naïve human donors with suspected inflammatory arthritis showed a reduced capacity to respond to adiponectin, which could be restored by the addition of PEPITEM. Further examination of whole blood indicated a lower bioavailability of PEPITEM in patients with early RA, leading the researchers to hypothesise that supplementation with PEPITEM could restore immune regulation and reduce the inflammatory changes seen in early-stage disease.
Their work in mouse models of inflammatory arthritis and gouty arthritis showed that injection of synthetic PEPITEM could prevent the onset of inflammatory arthritis, with significant reductions in disease incidence. In addition, joint swelling was reduced by PEPITEM when compared with infliximab - the current standard of care. Tissue studies confirmed that these changes were mirrored in synovial tissue (tissue inside the joints), with significantly less joint inflammation, cartilage damage, and bone erosion observed in PEPITEM treated mice, and significantly fewer white blood cells infiltrating the joints. Molecular studies showed significant down regulation of inflammatory mediators (NF-kB and COX2 protein) within the synovial tissue in PEPITEM-treated mice compared to controls, and a significant increase in the foxp3 transcript, which is crucial for the development of a type of white blood cell that suppresses the immune response, to prevent excessive inflammation and autoimmune disease.
View the full article at FightAging
