We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP) treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol exposures (twice a week for 4 wk) in guinea pigs. The animals were then anesthetized, tracheostomized, mechanically ventilated and challenged with ovalbumin aerosol. Maximal values of respiratory system resistance and elastance after antigen challenge were significantly lower in capsaicin-treated guinea pigs than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure resulted in a significant increase in lymphocytes and eosinophils both in bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with monoclonal antibodies revealed that most of the lymphocytes present in airway wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in airway wall significantly lower than non-capsaicin-treated guinea pigs (p < 0.005). This difference was not observed in eosinophil recruitment. Our results suggest that neurokinin release by sensory nerve terminals results in an amplification of the pulmonary inflammatory changes induced by chronic antigen exposure. In addition, neurokinins play a role in T-cell recruitment induced by chronic allergen exposure.

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction.Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals.Method: We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%).Results: We found that c-peptide (p = 0.006) and insulin (p = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs.Conclusion: Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.

No abstract