title: Participation of substance P distribution in the cytokine production of rheumatoid synovium.
abstract: Abstract Based on findings which suggested the involvement of the neuropeptide substance P in the pathogenesis of rheumatoid arthritis (RA), we investigated the mechanism of synovial pannus formation in RA, and examined the interaction between the cytokine production of synovial tissues and the concentration of substance P in the cartilage-pannus junction (CPJ). The CPJ and other peripheral synovial tissues were separately obtained from each part of the synovium from the knee joints of seven RA patients. The concentrations of substance P and the cytokines interleukin (IL)-1β and IL-6 in the CPJ and peripheral synovial tissues were determined by enzyme-linked immunosorbent assays. In addition, synovial cells were isolated from the CPJ and peripheral synovial tissues and treated with substance P or neurokinin-1 receptor antagonist to analyze the changes in cytokine production. The substance P levels were 211.2 and 50.5 pg/mg protein in the CPJ and the peripheral synovium, respectively. The IL-1β and IL-6 levels in the CPJ were 24.6 and 12.8 pg/mg protein, respectively. In the peripheral synovium, these levels were 4.3 and 2.5 pg/mg protein, respectively. In the CPJ, the IL-1β and IL-6 levels in tissue containing a high concentration of substance P (>200 pg/mg protein) were 39.4 and 21.6 pg/mg protein, respectively, and those in tissue containing a low concentration of substance P (≤200 pg/mg protein) were 11.6 and 5.1 pg/mg protein, respectively. Synovial cells from the CPJ produced higher levels of IL-1β and IL-6 than those from peripheral tissues. In addition, treatment of the cells with an NK-1 antagonist significantly reduced the production of these cytokines by the synovial cells. The theory that substance P plays a role in the pathogenesis of RA via the upregulation of cytokine production should be considered in further studies on the immunomodulatory properties of substance P in arthritis.
authors.affiliation: Department of Orthopaedic Surgery, Kansai Medical University , 10-15 Fumizono, Moriguchi, Osaka 570-8507 , Japan.
authors.forename: H
authors.initials: H
authors.lastname: Komuro
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Ogushi
authors.forename: S
authors.initials: S
authors.lastname: Takemura
authors.forename: Y
authors.initials: Y
authors.lastname: Toda
authors.forename: T
authors.initials: T
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Akagi
authors.forename: R
authors.initials: R
authors.lastname: Ogawa