Inflammatory compounds: Neuropeptide substance P and cytokines

Inflammatory diseases represent one of the major causes of morbidity and mortality throughout the world and they affect the functions of several tissues. The pathophysiology of these diseases involves release of many pro-inflammatory mediators such as cytokines/chemokines, histamine, C3a, C5a (complement components), bradykinin, leukotrienes (LTC4, LTD4, LTE4), PAF, and substance P, in addition to anti-inflammatory molecules. Recently, it has been demonstrated that neuroimmune interactions are important in the initiation and progress of inflammatory processes. Substance P is an 11-amino acid neuropeptide that is released from nerve endings in many tissues. It acts via membrane-bound NK1 receptors (NK1R). Inflammatory and neuropeptides such as substance P stimulate the release of chemokines, in particular IL-8, a potent neutrophil chemoattractant. Expression of IL-8 is regulated mainly by the transcription factors NF-kappaB, activating protein-1. Substance P plays an important role in immunological and inflammatory states, and it is a mediator of tissue injury, asthma, arthritis, allergy and autoimmune diseases. In this article, our studies revisited the interrelationship between these two powerful inflammatory compounds: substance P and cytokines. These observations suggest that these inflammatory molecules may represent a potential therapeutic target to treat several inflammatory states.