It is well known that allergic airways disease is characterized by inflammation and hyperresponsiveness, but the link between these two conditions has not been elucidated. We have previously shown that in allergic rhinitis, hyperresponsiveness is attributable to increased neural reactivity. We thus hypothesized that nerve growth factor (NGF), which is expressed by inflammatory cells and effects changes that lead to increased neural responsiveness, could be a pivotal mediator in this disease. Using reverse transcription-polymerase chain reaction (RT-PCR), Western immunoblotting, and ELISA to evaluate NGF expression and release, we found that subjects with allergic rhinitis have significantly decreased NGF mRNA in superficial nasal scrapings and significantly higher baseline concentrations of NGF protein in nasal lavage fluids, compared with control subjects. Nasal provocation with allergen significantly increased NGF protein in nasal lavage fluids of subjects with allergic rhinitis, but not of control subjects. The concentrations of NGF protein in nasal lavage fluids were not affected by provocation with the vehicle for allergen or with histamine. These data provide the first evidence of a steady state of dysregulation in mucosal NGF expression and release in allergic rhinitis, and support a role of this neurotrophin in the pathophysiology of allergic inflammatory disease of the human airways.

Stress is known to induce abortions, but underlying mechanisms are unknown. Both alloimmunization and injection of antibody to the asialoGM1 determinant of natural killer cells have been shown to prevent stress-triggered abortion in mice. DBA/2J-mated CBA/J female mice were used to investigate the influence of stress during early gestation on systemic hormone levels and on cytokines in the decidua that are thought to be relevant to abortion in nonstress-related murine abortion. Lowered levels of progesterone did not occur as a result of stress. In stressed mice, increased levels of the abortogenic cytokine tumor necrosis factor alpha (TNF alpha) were associated with decreased levels of pregnancy-protective transforming growth factor beta 2-related suppressive activity in uterine decidua. In the alloimmunized animals where stress failed to boost the abortion rate, these effects were abrogated. Production of TNF alpha may be stimulated by the neurotransmitter substance P (SP); after injection of an SP receptor antagonist or SP-antibody, stress failed to increase the abortion rate above the background level. The increased levels of TNF alpha we observed in the stressed animals were completely abrogated in the animals that had received the SP receptor antagonist; stress also failed to decrease the pregnancy-protective suppressive activity in the decidua of these animals. The data indicate that stress may inhibit protective suppressor mechanisms and promote secretion of abortogenic cytokines such as TNF alpha via neurotransmitter SP.

Background and AimsHigher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function.Design and MethodsThe study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters.ResultsCoronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24–5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07–29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24–66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03–1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001–1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96–0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters.ConclusionsExposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population.

Background: In allergic rhinitis, symptoms are triggered not only by allergens but also by environmental irritants. Hereinafter we address the hypothesis that this is reflective of increased responsiveness of the neural apparatus which, in turn, may be attributable to upregulation of nerve growth factor (NGF) in this disease. Methods: We compared subjects with active allergic rhinitis and healthy volunteers in terms of sensitivity and/or magnitude of three nerve–mediated responses, namely (1) the sneezing reflex induced by histamine, (2) the central or nasonasal reflex depicted by contralateral secretions induced by unilateral nasal challenge with capsaicin, and (3) the axonal reflex depicted by plasma extravasation upon capsaicin challenge. We have also measured NGF levels in nasal lavage fluids at baseline and with allergen provocation in rhinitis and healthy subjects. Results: Compared to healthy individuals, subjects with active allergic rhinitis were found to have (1) significantly greater sensitivity and reactivity of the sneezing reflex, (2) significantly greater secretory responsiveness to sensory nerve stimulation, and (3) significantly greater plasma extravasation indicated by albumin leakage following capsaicin nasal challenge. We also found that subjects with active allergic rhinitis have significantly greater baseline levels of NGF in nasal lavage fluids compared to their healthy counterparts, and that these levels can be increased by allergen nasal provocation. Conclusion: The responsiveness of the neural apparatus of the nose is significantly greater in patients with active allergic rhinitis. The increased presence of NGF in the nasal mucosa of these patients supports the hypothesis that this neurotrophin may be implicated in neural hyperresponsiveness.