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Neurokinin-1 Receptor Mediates Stress-Exacerbated Allergic Airway Inflammation and Airway Hyperresponsiveness in Mice

Ricarda A. Joachim, MD, Viktoriya Sagach, MD, David Quarcoo, MD, Q. Thai Dinh, MD, Petra C. Arck, MD and Burghard F. Klapp, MD

From the Department of Internal Medicine and Psychosomatics, Charité, Universitätsmedizin Berlin (R.A.J., V.S., T.D., P.C.A., B.F.K.) and the Department of Paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin (D.Q.), Berlin, Germany.



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  		Figure 1. Experimental protocol. After systemic sensitization on days 0, 14, 21 (ovalbumin (OVA) i.p.) mice were challenged twice with OVA aerosol on days 26 and 27. Coinciding with the first challenge, the stress groups (II and IV) were exposed to sound stress for 24 hours, while nonstressed mice remained undisturbed. On days 26 and 27, groups III and IV received an IP injection of the neurokinin (NK)-1 receptor antagonist before airway challenge.

 


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  		Figure 2. Total leukocyte number and cell type identification in bronchoalveolar lavage (BAL) fluids of OVA-sensitized and airway-challenged BALB/c mice. BAL was performed 24 hours after last allergen aerosol challenge. Stressed mice that were treated with phosphate-buffered saline (PBS) showed significantly higher total cell numbers than nonstressed PBS-injected mice, *p < .017. Application of neurokinin-1 receptor antagonist (NK-1-RA) in stressed mice abrogated the stress-induced increase, #p = .023. Columns represent mean and SEM (Leuko = leukocytes, Lympho = lymphocytes, Eos = eosinophil granulocytes, Gran = neutrophil granulocytes, Macro = Macrophages).

 


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  		Figure 3. Effect of stress on airway reactivity measured in ovalbumin (OVA)-sensitized and airway-challenged BALB/c mice. The frequency that caused 50% of maximal contraction (ES50) was calculated. Mean ES50 from the nonstressed group I was set as 100%. Airway reactivity was higher in stressed mice treated with phosphate-buffered saline (PBS) compared with nonstressed mice, #p = .024. Application of neurokinin-1 receptor antagonist (NK-1-RA) in stressed mice significantly abrogated the stress-induced increase. *p < .017. Indicated are mean and SEM from 7 to 9 mice per group.

 




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