Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P.

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. Recently, the involvement of neuropeptides has been demonstrated to play an important role in the inflammatory cascade. Neuropeptides such as Substance P are released by cutaneous neurons and modulate the function of immunocompetent and inflammatory cells as well as epithelial and endothelial cells. Substance P has been shown to function as a mediator for cell proliferation, cytokine production, and as an upregulator of various cell surface receptors. In this study, we show the effect of Substance P on the production of Tumor Necrosis Factor-alpha, Interleukin 1-beta, Interleukin 2, and Interleukin 6 by T-lymphocytes, macrophages and neutrophils. These data demonstrate that pathophysiological levels of Substance P induce production of cytokines in all three cell populations tested. Interestingly, T-cells demonstrated the highest percentage of cells expressing all four cytokines. In contrast, macrophages and neutrophils produced the highest absolute levels of cytokines. The elucidation of mediating mechanisms of Substance P activation of leukocytes is crucial to the understanding of the cutaneous inflammatory cascade and involvement of the peripheral nervous system on the immune system. These findings suggest that Substance P participates in the complex network of mediators that regulate cutaneous inflammation and potentially the rate of wound healing.