Pulmonary chemoreflex responses are potentiated by tumor necrosis factor-alpha in mice.

Abstract

Inhalation of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine, induces airway hyperresponsiveness, and the underlying mechanism is not fully understood. Hypersensitivity of vagal bronchopulmonary C-fiber afferents is known to contribute to the airway hyperresponsiveness during an airway inflammatory reaction. Because activation of these afferents can elicit pulmonary chemoreflexes, this study was designed to determine if a pretreatment with TNF-α induced airway inflammation and enhanced the pulmonary chemoreflex sensitivity in anesthetized mice; and if so, whether the effect was mediated through activation of either or both of the TNF receptors, p55 and p75. Our results showed that TNF-α instilled into the lung caused an increased sensitivity of pulmonary chemoreflex responses to various chemical stimulants of the vagal bronchopulmonary C-fiber afferents. The increased sensitivity was found 24 h later, persisted at 48 h, and then gradually declined after several days. The TNF-α-induced airway hypersensitivity was accompanied by airway inflammation as shown by a striking elevation of the levels of eosinophils and neutrophils, several potent bronchoactive inflammatory mediators, and proinflammatory cytokines in the bronchoalveolar lavage fluid. Furthermore, the increase in pulmonary chemoreflex response caused by TNF-α was partially abrogated in both p55-null and p75-null mice, but completely abolished in p55/p75-null mice. In conclusion, TNF-α pretreatment induced airway inflammation and a sustained elevation of pulmonary chemoreflex sensitivity, which was mediated through an activation of both types of TNF receptors.

• Authors: Ruei-Lung Lin, Yu-Jung Lin, Marcus J Geer, Richard Kryscio, Lu-Yuan Lee
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 114 Issue 11 Pg. 1536-43 (Jun 2013) ISSN: 1522-1601 [Electronic] United States
• PMID: 23539315 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha

Topics

• Administration, Inhalation
• Animals
• Chemoreceptor Cells (immunology, radiation effects)
• Lung (drug effects, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pneumonia (chemically induced, immunology)
• Receptors, Tumor Necrosis Factor (immunology)
• Reflex (drug effects, immunology)
• Tumor Necrosis Factor-alpha (administration & dosage, immunology)