LTB4 and BLT1 in inflammatory arthritis

Abstract

Inflammatory arthritis, including rheumatoid arthritis (RA), is characterized by infiltration of inflammatory cells into the joints. Biological agents targeting TNF-α and IL-6 dramatically improve RA. However, some RA patients do not respond to current treatments and these broadly active upstream biological agents increase the risk of severe infection. Therefore, there remains a need for other effective and safe treatments for RA. Many studies have implicated that blockade of leukotriene B4 (LTB₄) and its high affinity receptor BLT1 dramatically suppress arthritis in animal models. In addition, levels of LTB₄ in serum, synovial fluid and synovial tissue are increased in RA patients compared to healthy donors or osteoarthritis patients. These data suggest that LTB₄ and BLT1 likely contribute to the pathogenesis of human RA. However, several clinical trials inhibiting BLT1 in RA were not successful. Our recent data revealed that LTB₄ is a key mediator in a complement, lipid, cytokine and chemokine cascade that first initiates and then sustains neutrophilic inflammation in inflammatory arthritis. These new mechanistic studies suggest novel ways to target the LTB₄-BLT1 pathway for the treatment of RA and other inflammatory diseases.

Keywords: Inflammatory arthritis; Leukocytes; Leukotriene B4; Leukotriene B4 receptor; Rheumatoid arthritis.