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Background: Neurogenic inflammation may participate in the development and progression of bronchial asthma. The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as neurokinin A (NKA) and substance P. Tachykinins are secreted from sensory airway nerves and inflammatory cells after allergens exposure. In clinical practice, assessment of airway inflammation is difficult. Therefore, detection of biological markers of airway inflammation in sputum might offer help for proper monitoring of asthma severity., Aim of the Study: We aimed to measure sputum NKA in relation to acute asthma exacerbations of varying severity., Methods: Sputum NKA was measured by enzyme-linked immunosorbent assay in 24 children and adolescents during and after acute asthma exacerbation and 24 healthy matched controls., Results: Sputum NKA was significantly higher in asthmatic patients during acute exacerbation than controls [217.5 (284) vs 10 (7) ng/ml, P < 0.001]. When patients with acute asthma exacerbation were followed-up till remission, sputum NKA levels decreased significantly, but they remained significantly higher than controls. Sputum NKA levels were significantly higher in severe than moderate and in moderate than mild exacerbations, and was negatively correlated to peak expiratory flow rate (r = -0.9, P < 0.001). Sputum NKA had significant positive correlations to eosinophil counts in blood and sputum (r = 0.6, P < 0.001 and r = 0.7, P < 0.001 respectively)., Conclusions: Sputum NKA is up-regulated during acute asthma exacerbation and it positively correlates to its severity. Thus, NKA may aid in objective classification of the exacerbation severity. In addition, NKA may be a target for new asthma therapy.

The aim of this study was to investigate the presence of substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) in the gingival crevicular fluid of teeth diagnosed with pain of pulpal origin compared with clinically healthy teeth, and to detect any changes in the levels of these neuropeptides in gingival crevicular fluid after removal of the pulp from the painful teeth. Gingival crevicular fluid was collected at baseline from one interproximal site at a painful and a non-painful contralateral tooth from 54 adult patients. Sampling was repeated after 1 wk in a subset of 21 subjects. Samples were analysed for SP, NKA, and CGRP using radioimmunoassay. The mean levels of SP and NKA were significantly higher in gingival crevicular fluid from painful teeth compared with non-painful teeth. The level of SP in the GCF of painful teeth fell significantly 1 wk after pulpectomy. In contralateral teeth, there were no significant differences in the levels of SP and NKA after 1 wk. It is concluded that SP and NKA are present in significantly greater amounts in the GCF of painful teeth compared with healthy teeth.

Background: The study of periodontitis provides a unique model for assessing the involvement of neuropeptides in inflammatory disease., Aim: To investigate the effects of periodontal treatment, resulting in a return to periodontal health, on the levels of substance P (SP) and neurokinin A (NKA) in gingival crevicular fluid (GCF)., Method: We completed a cause of non-surgical treatment for 8 subjects with periodontitis (6 females 2 males, mean age 45.1, range 38-67 years) started a course of non-surgical periodontal treatment. Clinical indices were measured at 2 periodontitis sites at the initial visit and at 8 weeks after the completion of treatment in each subject. A 30-s sample of GCF was collected from each test site using perio paper strips. Each strip was placed into 500 microl of ice cold 0.1 M PBS, pH 7.4, vortex mixed for 30 s, and then stored at -70 degrees C until analysed by radioimmunoassay., Results: The clinical condition of all test sites improved as a result of the periodontal treatment. The levels (pg/30 s sample) of SP fell from 56.3 (SD 66.0) at the initial visit to 4.2 (3.1) after treatment, p=0.017. The concentration (pg/microl) of SP in GCF fell from 140.6 (175.6) to 24.2 (11.1), p=0.036. The levels of NKA fell from 30.5 (17.1) to 10.6 (4.9), p=0.012 whereas the concentration changed little from 85.4 (43.5) to 61.6 (15.1), p=0.41., Conclusion: The reduction in inflammation resulting from effective periodontal treatment is associated with a reduction in the levels of tachykinins in gingival crevicular fluid.

The aims of the present study were to investigate whether the tachykinins substance P and neurokinin A were present in gingival crevicular fluid in both periodontal health and disease and to study the relationship with periodontal inflammation. Gingival crevicular fluid (GCF) was collected from a healthy, a gingivitis and a periodontitis site in 20 subjects with periodontitis and from a healthy site in 20 subjects without periodontitis. The volume of GCF was measured and each sample subsequently analysed for substance P and neurokinin A by radioimmunoassay. There were significantly increased levels of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) in gingivitis and periodontitis sites compared with healthy sites. Both tachykinins were significantly elevated in periodontitis affected subjects, with significantly more tachykinin-like immunoreactivity at healthy sites in periodontitis affected compared with periodontally-healthy subjects. Despite the considerable individual variation in the levels of SP-LI and NKA-LI, both tachykinins were present at levels at which they could have biological activity. It is concluded that substance P and neurokinin A may have a rôle in the pathogenesis of periodontal disease and that further investigations could prove useful in clarifying the mechanisms through which neuropeptides could modulate periodontal health and disease.

We recently demonstrated that cultured malignant schwannoma (MS)-derived cells can support human skin mast cell (HSMC) survival in vitro. Cultured HSMCs were spindleshaped in close contract with MS-derived cells, suggesting cell to cell interaction. To elucidate the mechanism of the enhanced HSMC survival in coculture with MS-derived cells and the cellular interactions between HSMC and MS-derived cells, we examined the immunocytochemical characteristics of MS-derived cells using immunofluorescence. Morphologically, cultured MS-derived cells were polygonal with abundant cytoplasm and resembled perineurial cells. The cultured cells immunoreacted positively with vimentin, fibronectin, laminin and collagen IV, but negatively with anti-S100 protein, anti-neuron specific enolase, and anti-neurofilament (68 kd, 145 kd, 200 kd) antibodies. MS-derived cells were distinct from Schwann cells in their lack of S100 protein and also distinguishable from endoneurial fibroblasts that produce fibronectin, but never expressed laminin or collagen IV. MS-derived cells thus possess the characteristics of perineurial cells in their general morphology and their immunocytochemical properties. Immunoreactivity for substance P (SP) and neurokinin A (NKA) was found in the cytoplasm of these cells, particularly around the nuclei. Vasoactive intestinal peptide, somatostatin, and calcitonin gene related peptide were negative. From these findings, we characterized the MS-derived cell's in vitro properties and concluded that it is similar to a perineurial cell. The extracellular matrix protein, laminin, and fibronectin expressed in the MS-derived cell might contribute to HSMC survival and morphology through cell to matrix adhesion. Neuropeptides such as SP and NKA, expressed in the MS-derived cell, might play some role in enhanced HSMC survival in vitro.

The interaction between the nervous system, immune system and bronchial reactivity was studied in rats by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.