Upregulation of tumor necrosis factor-alpha by stress and substance p in a murine model of allergic airway inflammation.
OBJECTIVE
Clinical observation has suggested that stress and asthma morbidity are associated, though underlying mechanisms are not clearly understood. After having established a mouse model of stress-exacerbated allergic airway inflammation, we demonstrated a stress-mediating role for neurokinin-1 receptor, the main substance P (SP) receptor. Here, our aim was to investigate the influence of stress or exogenously applied SP on airway inflammation and on the local cytokine production of immune cells.


METHODS
BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly challenged with OVA aerosol. Sound stress was applied to the animals for 24 h, starting with the first airway challenge. Alternatively, one group of non-stressed mice received intranasal SP before airway challenges. Cell numbers were determined in bronchoalveolar lavage (BAL) fluid. Leukocytes from mediastinal lymph nodes were analyzed by flow cytometry to determine the percentages of T cells producing interleukin-4, interferon-gamma and tumor necrosis factor-alpha.


RESULTS
In BAL fluids of stressed or SP-treated animals, significantly higher total cell counts were found compared to non-stressed mice. In lymph nodes, the percentage of TNF-alpha-positive T cells was higher in stressed mice and mice after application of SP. In contrast, the influence of stress did not increase the percentages of interferon-gamma-positive CD3+ cells, meanwhile the application of SP increased the percentages of T cells positive for this cytokine.


CONCLUSIONS
Our data provide further evidence for a stress-mediating neuroimmunological pathway that, putatively via SP, is able to influence the composition of immune cells in different compartments of allergic airway inflammation.
Joachim
Ricarda A
RA
Department of Internal Medicine and Psychosomatics, Charité - Universitätsmedizin Berlin, Berlin, Germany. ricarda.joachim@charite.de
Sagach
Viktoriya
V
Quarcoo
David
D
Dinh
Thai
T
Arck
Petra C
PC
Klapp
Burghard F
BF
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D017252:CD3 Complex / Q000276:immunology; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology; D013016:Sound / Q000009:adverse effects; D013312:Stress, Physiological / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D013373:Substance P / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D017252:CD3 Complex; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D013373:Substance P; D007371:Interferon-gamma