Regulation of p38 MAP kinase in CD4 lymphocytes by infliximab therapy in patients with rheumatoid arthritis

Decreased ex vivo production of TNF-α and IL-8 by peripheral blood cells of patients with rheumatoid arthritis after infliximab therapy

“…This TNF-α blocker has been shown to have an estimated half-life of 8 to 9.5 days in serum after a 3 mg/kg dose and its serum concentration decline more slowly when the drug is given in combination with disease-modifying anti-rheumatic drugs such as MTX [24]. Garfield and coworkers have previously demonstrated that infliximab has no effect on the number of PBMC [25]. After infliximab treatment, the activated p38 MAP kinase (MAPK) level in CD4+ T cells was markedly reduced while the level of total p38 MAPK and the number of TNF-α producing cells were unchanged [25,26].…”

“…Garfield and coworkers have previously demonstrated that infliximab has no effect on the number of PBMC [25]. After infliximab treatment, the activated p38 MAP kinase (MAPK) level in CD4+ T cells was markedly reduced while the level of total p38 MAPK and the number of TNF-α producing cells were unchanged [25,26]. Therefore, our study showed that infliximab exhibited an inhibitory effect on the circulating peripheral blood cells to release TNF-α upon stimulation, probably through the suppression of the activity of p38 MAPK in PBMC.…”

Immunomodulatory effects of statins and autoimmune rheumatic diseases: Novel intracellular mechanism involved

“…Recently, it has been postulated that Ras-mediated signaling pathways are involved in the activation of RA synovial fibroblasts and the destruction of bone in arthritic joints [127]. Specifically, Garfield et al [131] demonstrated that the CD4 + cells from RA patients treated with infliximab showed a decline of active p38 MAPK. This pathway is associated with IFN-γ production [90].…”

“…This inhibition of p38 MAPK can reduce inflammation in animal models and RA, suggesting that p38 MAPK cascade plays a role in the pathogenesis of inflammatory arthritis [156][157][158][159]. Garfield et al [131] demonstrated that anti-TNF-α treatment in RA patients decreased the levels of active p38 MAPK in CD4 + T-cells without effect of this pathway in other cells (macrophages and CD8 + T-cells). They proposed that TNF-α in RA patients increase p38 MAPK in CD4 + T-cells, thereby, promoting INF-γ and TNF-α production.…”

Tyr323-dependent p38 activation is associated with rheumatoid arthritis and correlates with disease activity

“…T cell functions associated with RA progression, including the Th1 immune response, are controlled by p38 (7,37). Although it has long been assumed that p38 activity is regulated mainly through the classic MAPK pathway, the Tyr 323 -dependent pathway is required for TCR-mediated p38 activation (26,30).…”