Low plasma concentrations of VIP and elevated levels of other neuropeptides during exacerbations of asthma

Abstract

Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory cells. Their widespread distribution and physiological effects suggest that they may play important roles in asthma. We investigated whether, during an exacerbation of asthma, patients displayed changes in plasma levels of the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25 adult patients attending the emergency ward with an exacerbation of asthma was sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY-like immunoreactivity (-LI) were determined by immunoassay, and the results obtained were compared with findings in 21 healthy controls. The mean plasma levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1), SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1, respectively). A relationship was seen between the reversibility of obstruction, expressed as improvement of peak expiratory flow upon treatment, and the neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and CGRP-LI in particular, may therefore be employed as predictors of responsiveness to bronchodilatory therapy.

Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness

“…Moreover, Npy polymorphisms are associated with increased risk for asthma in overweight subjects (18,25). Other reports have demonstrated that plasma levels of NPY were increased in asthmatics at rest and in acute exacerbations (26)(27)(28). Our study shows that increased expression of Npy in airway epithelium can induce an AHR phenotype in a paracrine manner (Supplemental Figure 6).…”

Differential Effects of Neuropeptides on Cytokine Production by Mouse Helper T Cell Subsets

“…Since higher peripheral blood NPY, SP and CGRP concentrations and lower VIP levels have been found in bronchial asthma patients compared to normal subjects [30], it is possible that they can exacerbate the symptoms through favoring the Th2 balance. This is also consistent with the findings concerning multiple sclerosis (MS) which is thought to be associated with an excessive Th1 response.…”

The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

“…Upregulation of VIP was detected in neurogenic inflammation in the rat retina (Bronzetti et al, 2007). Plasma VIP level of patients with acute asthmatic exacerbations was found to be significantly lower compared to the controls and showed correlation with the response to therapy, suggesting that bronchodilatory and vasodilatory actions of the peptide are essential in this regard (Cardell et al, 1994;Said, 1982). Even in a human study, VPAC2 receptor was shown to exert inhibitory action against bronchial asthma (Lind en et al, 2003).…”