Effects of Central and Peripheral Administration of Neuropeptide S on the Level of Serum Proinflammatory Cytokines in Pigs

Abstract

Objectives: The recently discovered neuropeptide S (NPS) and its cognate receptor represent a novel system of neuromodulation and are involved in many physiological and pathological processes. NPS has been implicated in the regulation of proinflammatory cytokine secretion in the pulmonary alveolar macrophages (PAMs) of pigs in vitro. In this study, we tested the hypothesis whether either central or peripheral injection of NPS would stimulate the secretion of the proinflammatory cytokines in pigs. Methods: In experiment 1, pigs were fitted with an intracerebroventricular cannula and indwelling jugular catheters, and were then randomly assigned to receive 10 or 30 nmol NPS in artificial cerebrospinal fluid. In experiment 2, pigs were fitted with indwelling jugular catheters, and randomly received 15 or 30 nmol NPS in saline. Serial blood samples were collected every 10 min for 1 h before and for 2 h after injections, and serum concentrations of IL-1β, IL-6 and TNF-α were determined. Results: Serum concentrations of these cytokines were increased in pigs that received central and peripheral injection of NPS, and the elevated secretion of these cytokines was in a time- and concentration-dependent manner. Conclusion: The level of serum proinflammatory cytokines could be activated by both central and peripheral administration of NPS in a dose- and time-dependent manner in the pig. The present data support the concept that NPS may be considered as a potent modulator for the immune system and may play an important role in the inflammation and immune system of pigs.

Screening for potential serum biomarkers in rat mesangial proliferative nephritis

“…It was reported that increased serum VGF might represent a useful biomarker for the diagnosis of subclinical hypocalcemia in cows . NPS is a potent modulator of the immune system, and was reported to play an important role in inflammation and immunity in pigs . We suspect that serum VGF and NPS may be related to metabolism and immune system function in anti‐Thy1 nephritis.…”

Plasma Neuropeptide-S Levels in Population with Generalized Anxiety Disorder: A Controlled Study

“…Although the rodent and experimental studies that investigated the role of NPS/NPSR in the central nervous system reported that NPS is associated with robust anxiolytic effects, it has also been implicated in a few other prominent neuro-chemical processes, including the activation of HPA axis and modulation of pro-inflammatory cytokines, the neuroendocrinological systems related to anxiety-related disorders (12,23,24). Additionally, a recent study discovered a naturally-occurring gene polymorphism of NPSR that is involved in distorted sympathetic arousals and anxiety-related emotional processes in people afflicted with panic disorders (PD) (14) In GAD, somatic symptoms associated with adrenergic hyperactivity, such as palpitations, nausea, sleep disturbances, sweating, are the most commonly encountered symptoms which are similar to those experienced in PD.…”

“…In addition to NPS's in the central nervous system, in vivo studies conducted on animals revealed that the NPS/NPSR system is associated with the modulation of proinflammatory cytokines. Moreover, NPSR gene polymorphism was demonstrated to be associated with some systemic chronic gastrointestinal and respiratory diseases, since some animal studies have demonstrated that the NPS/NPSR system is distributed in the peripheral system, including the immune tissues, thyroid, mammary, and salivary glands (10,12). While limited studies have been conducted on humans to investigate the role of NPS in psychiatric conditions, some reports support NPS/NPSR system's potential involvement in anxiety disorders, such as panic disorder (13,14).…”

Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma

“…The upregulation of NR4A1 and FOS induced by the combination of NPS-Val(6) and NPSR1-Ile(107) is anticipated not only to interact in a feedback loop with their regulatory elements in NPSR1 but also to regulate a number of other target genes including those involved in immune responses. For instance, the levels of serum pro-inflammatory cytokines could be activated by both central and peripheral administration of NPS in pigs [44], and NPS has shown direct effects on phagocytosis [45] [46] and chemotaxis [47] [48]. Further insights to immune responses are suggested by the upregulation of CXCL2 and CCL20 encoding chemokine receptors ligands (Fig 2) .…”