Disturbed immunoregulatory properties of the neuropeptide substance P on lymphocyte proliferation in HIV infection

Abstract

SUMMARY The neuropeptide substance P (SP) is known to increase cell‐mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP. may represent a model for the analysis of Immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10−10 10−6) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by3H‐thymidine incorporation in peripheral blood lymphocytes from 34 HIV‐infected patients (16 asymptomtic (ASY) persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/ PGL HIV‐infected patients, SP 10−7M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A. in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide‐dependent immunoregulatory systems in HIV infection.

The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders

“…In addition, this neuropeptide can also inhibit the production of the immunosuppressive cytokine TGF-β1 by activated macrophages (Marriott and Bost, 1998) providing another mechanism by which this tachykinin can foster an inflammatory environment. Furthermore, substance P has been reported to stimulate T-lymphocyte proliferation and natural killer cell activity, and substance P may also serve as a B-lymphocyte differentiation cofactor and augment immunoglobulin secretion (Croitoru et al, 1990; Pascual and Bost, 1990; Pascual et al, 1991a,b, 1992; Bost and Pascual, 1992; Covas et al, 1994). As such, these studies indicate that this neuropeptide has the potential to exacerbate both acute and chronic inflammatory immune responses associated with the recruitment of immune cells to the CNS.…”

Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment

“…It inhibits the cytokine TGF-β1, which is an immune-suppressor, released by macrophages [32] and thus promotes inflammation. It also induces the proliferation of T-lymphocytes, B-lymphocytes and natural killer cells, resulting in immunoglobulin secretion [33] . IFN-γ and TNF-α can activate the upregulation of NK-1R in macrophages like IL-4 [34] .…”

Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia

“…SP and NKA preferentially bind to the G protein-coupled NK-1R and NK-2R, respectively [6]. SP enhances cytokine secretion from lymphocytes, monocytes, macrophages, and mast cells [7][8][9][10][11][12][13][14][15]. Furthermore, SP-induced release of inflammatory mediators such as cytokines and histamine potentiates tissue injury and further stimulates leukocyte recruitment, thereby amplifying the inflammatory response [16].…”