The tachykinins neurokinin A and physalaemin stimulate murine thymocyte proliferation

The tachykinins constitute a family of neuropeptides that are released from sensory neurons, mediating a variety of responses termed neurogenic inflammation. The present study investigates the possibility that tachykinins are also involved in immune-regulatory mechanisms. The mammalian tachykinins neurokinin A (NKA), neurokinin B, neuropeptide K and substance P, as well as the nonmammalian tachykinin physalaemin (PHY) and eledoisin, were analysed in 10-pM to 1.0 microM concentrations for regulatory influences in several lymphocyte proliferation assays. NKA, and to a lesser extent PHY, but none of the other tachykinins tested, displayed a stimulatory action in murine thymocyte cultures, utilised as an interleukin-1 (IL-1) bioassay. The effect was apparent only at a concentration of 0.1 microM or higher. No further stimulatory effect of the tachykinins could be observed in thymocyte cultures already suboptimally stimulated to proliferation by addition of IL-1. The tachykinins had no effect in direct and co-mitogenic T and B lymphocyte proliferation assays with rat spleen cells, in a thymocyte growth peptide assay with mouse thymic lymphoblasts or in an interleukin-2 (IL-2) bioassay with IL-2-dependent rat splenoblasts. Our findings indicate that NKA and PHY can act as immune regulators. The results are relevant for the understanding of the interaction between the nervous and the immune system, and are of particular interest in view of the inflammatory actions of both tachykinins and IL-1.