LTB4 and BLT1 in inflammatory arthritis. (October 2017)

• Record Type: Journal Article
• Authors: Miyabe, Yoshishige; Miyabe, Chie; Luster, Andrew D.
• Is Part Of: Seminars in immunology. Volume 33(2017)
• Page Start: 52
• Page End: 57
• Publication Date: 2017-10
• Subjects: Leukotriene B4 -- Leukotriene B4 receptor -- Rheumatoid arthritis -- Inflammatory arthritis -- Leukocytes; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Immunity -- Periodicals; Immunologie -- Périodiques; Electronic journals; 616.079
• DOI: 10.1016/j.smim.2017.09.009
• Languages: English
• ISSNs: 1044-5323

Abstract

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.