Role of lymphocyte activation by substance P in rheumatoid arthritis

Peripheral mononuclear cells taken from rheumatoid arthritis (RA) patients, which had previously been treated in vitro with the neuropeptide Substance P (SP) followed by stimulation with the mitogen PHA, showed a significantly higher percent positivity of lymphocytes with the double-markers CD4+ CD2+, CD8+ CD25+, CD4+, HLA-DR+ and CD8+ HLA-DR+ than those of the cells untreated by SP. No effect of SP was detected in normal controls, except that the cells with the double-marker CD4+ CD25+ were slightly increased. Furthermore, in RA patients the percentage of CD4+ CD45R- cells was increased, while that of CD4+ CD45R+ cells was decreased, by pre-treatment with SP and stimulation with PHA. Monocytes of patients with rheumatoid arthritis after the treatment with SP released a significantly higher amount of oxygen-intermediate than those of normal controls with or without SP. From these results, it could be considered that SP plays an important role in RA inflammation.