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Interleukin-1B-induced airway hyperresponsiveness (AHR) in ferrets enhances substance P (SP) in intrinsic airway neurons.
Wu ZX; Satterfield BE; Fedan JS; Dey RD
Am J Respir Crit Care Med 2001 Apr; 163(5)(2)(Suppl):A626
Interleukin-1B (IL-1B) causes airway inflammation, enhances airway smooth muscle responsiveness and alters neurotransmitter expression in sensoryl, sympathetic and myenteric neurons. The aim of this study was to examine the role of intrinsic airway neurons in AHR induced by IL-1B. Ferrets were instilled intratracheally with IL-1B (0.3 ug/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and SP expression in tracheal neurons was assessed. After IL-1B treatment, tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) was significantly increased (EC50's: 0.91 to 0.37 uM for ACh and 0.43 to 0.20 uM for MCh in control and IL-1B, respectively), as were smooth muscle contractions to electric field stimulation (EFS) at 10 Hz (from 27% to 34% of maximal ACh contraction) and 30 Hz (37% to 44%). The IL-1B-induced AHR was maintained in tracheal segments cultured for 24 hr, a procedure shown to deplete sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, a NK1-receptor antagonist, attenuated the IL-1B-induced increase in reactivity to ACh and MCh and to EFS in cultured tracheal segments. In contrast, CP-99994 had no effect after saline-treatment. The number of SP-containing neurons in longitudinal trunk (LT) and innervation of superficial muscular plexus (SMP) neurons increased significantly after treatment with IL-1B. These results show that the enhanced airway smooth muscle contractile responses induced by IL-1B are mediated partly by SP and may result from increased SP-production by LT neurons and enhanced SP-innervation of SMP neurons.
Laboratory-animals; Animals; Animal-studies; Airway-obstruction; Airway-resistance; In-vitro-studies
Issue of Publication
American Journal of Respiratory and Critical Care Medicine. Abstracts of the American Thoracic Society 2001 International Conference, May 18-23, 2001, San Francisco, California
Page last reviewed: July 9, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division