Participation of substance P distribution in the cytokine production of rheumatoid synovium.

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)-1ß 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-1ß 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-1ß 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-1ß 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.

Early detection of left atrial thrombus in acute cardiogenic cerebral embolism by transesophageal echocardiography.

Re-embolization tends to occur during the first 14 days after the onset of cardiogenic cerebral embolism. The usefulness of early transesophageal echocardiography (TEE) was investigated in 64 patients (33 men and 31 women, mean [+/-SD] age 70.1 +/- 12.6 years) who underwent TEE within 30 days of the onset of cardiogenic cerebral embolism. Patients were retrospectively classified into two groups based on the time from the onset of the embolism to performance of TEE: group A consisted of 33 who underwent TEE within 4 days of the onset and group B consisted of 31 who underwent TEE 5 to 30 days after the onset. Transthoracic echocardiography visualized a left atrial thrombus in two patients, and TEE detected thrombi in 14 patients: 11 in group A and 3 in group B. Lethal re-embolization occurred in two patients in group A who had highly mobile thrombi. Early TEE may be useful for detecting left atrial thrombi and predicting the risk of re-embolization in patients with acute cardiogenic cerebral embolism.