Finally, we elucidate the effect of P2-1 on the HMGB1-induced release of pCTS-L and other cytokines and chemokines using primary human peripheral blood mononuclear cells (PBMCs).<h4>Results</h4>P2-1 significantly improved survival and reduced systemic inflammation in a sepsis model, and attenuated arthritis severity and pain sensitivity in an RA model, even with therapeutic administration after disease onset. Here, HMGB1 is linked to arthritic joint disease.