Neuropeptide substance P and the immune response

Abstract

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response.

Antiinflammatory effects of aprepitant coadministration with cART regimen containing ritonavir in HIV-infected adults

“…A number of changes detected by SOMAscan are consistent with observations of the proinflammatory role of SP (9,52,53) and our hypothesis of the antiinflammatory effect of aprepitant. We detected a decrease in IL-6 levels -an important cytokine in chronic, HIV-associated inflammation -although to a lesser extent than in the previous study.…”

Substance P and pain chronicity

“…SP is also expressed by a variety of non-neuronal cell types such as microglia, as well as immune cells such as T cells, tissue-resident macrophages, dendritic cells and eosinophils. SP is known to play a key role in immune cell migration and expression of chemokines and adhesion molecules (Mashaghi et al 2016). Factors released from neuronal and non-neuronal elements have been recognized as mediators of persisting pain (Guo et al 2007; Xanthos and Sandkühler 2014; Totsch and Sorge 2017).…”

“…In contrast to receptors for classical transmitters, such as glutamate (Parsons et al in Handb Exp Pharmacol 249–303, 2005), only a minority of neurons in certain brain areas express neurokinin receptors (NKRs) (Mantyh in J Clin Psychiatry 63:6–10, 2002). SP is also expressed by a variety of non-neuronal cell types such as microglia, as well as immune cells (Mashaghi et al in Cell Mol Life Sci 73:4249–4264, 2016). SP is an 11-amino acid neuropeptide that preferentially activates the neurokinin-1 receptor (NK1R).…”

Arzneimittelassoziierte Angioödeme

“…Substanz P wird durch ACE, NEP und DPP-IV degradiert [23,27]. Bei einer Hemmung von ACE erfolgt die Degradierung primär durch DPP-IV [25,34,35]. [4,37,38].…”