Chronic unpredictable stress exacerbates allergic airway inflammation in mice.

Background: Chronic stress triggers asthma exacerbations and is deleterious to many other diseases, but the mechanisms remain elusive. We hypothesize that, given stress exposure releases a multitude of molecules capable of modifying immune and neuronal function, asthma exacerbation would result from altered neuroimmune communication in the lungs. Aims and objectives: 1) To establish a model for chronic stress exposure in asthma 2) To describe mechanisms linking stress and airway inflammation Methods: We applied a 12-day chronic unpredictable stress (CUS) paradigm followed by ovalbumin (OVA) exposure. 24h later, the animals had their lungs and dorsal root ganglia (DRG) harvested. Results: BAL cellularity was increased in CUS, OVA, and OVA+CUS groups compared to PBS control. However, OVA+CUS showed significantly higher count than OVA. Compared to PBS and OVA, OVA+CUS lung sections displayed heightened peribronchial infiltration and goblet cell number. OVA+CUS mice displayed increased VCAM-1 and p-iκBα in the lungs and increased p-NFκB p65 and P2X3 in DRG. ELISA showed increased levels of IL-6 in serum and IL-33 in lungs of OVA+CUS. Via RT-PCR, IL-4 and IL-13 were similarly elevated in OVA and OVA+CUS; nonetheless, IL-6 was uniquely increased in OVA+CUS. Neurotrophin gene expression revealed increased BDNF expression in CUS, OVA, and OVA+CUS groups. However, its receptor, TrkB, was only elevated in CUS and OVA+CUS. Conclusion: CUS exacerbated allergic lung inflammation in mice. Our results showed modulation of molecules related to immune and neuronal functions, such as TrkB, IL-6, and P2X3. Future experiments shall determine neuron-immune cell contact alterations in stress-exposed animals.