Inhibitory effect of NSAIDs on the chemotaxis induced by substance P on human monocytes and polymorphonuclear cells

Substance P is involved in the modulation of arthritic pain, and more recently it has been suggested that substance P might be involved also in the immunological aspects of arthritic diseases. Substance P is present in the synovial fluid of arthritic patients, where it can induce the chemotaxis of polymorphonuclear cells (PMN) and monocytes, and the synthesis of cytokines. We thought it worthwhile to investigate the effect of non steroidal anti-inflammatory drugs (NSAIDs) on the chemotactic effect of substance P on PMN and monocytes. We evaluated the effects of NSAIDs on the chemotactic effect of two concentrations of substance P that are well within those reached by the neuropeptide in arthritic diseases. The different NSAIDs inhibit the chemotactic response of PMN with different patterns, while the effect on the chemotaxis of monocytes is much weaker. The data we present suggest that the effect of NSAIDs on the development and progress of arthritic disease could involve their capacity of blocking the chemotactic activity of substance P, and with mechanism interfere with the self-feeding pathological circle of substance P. It remains to be determined whether the effect is mediated by the block of cyclooxygenase or other less specific effects of NSAIDs on PMN and monocyte membranes.