Respiratory syncytial virus (RSV) infection is associated with exaggerated neurogenic inflammation in the airways. This study sought to determine whether irritation of the mucosal sensory fibers affects the recruitment of lymphocytes and monocytes to RSV-infected airways. Pathogen-free rats were inoculated with RSV or with virus-free medium and were injected 5 days later with capsaicin to stimulate airway sensory nerves. Bronchoalveolar lavage was performed 1, 5, or 10 days after nerve stimulation, and samples were analyzed by differential cell count and flow cytometry. Without nerve stimulation, RSV caused a minimal increase in the number of lymphocytes and monocytes above pathogen-free control levels. After nerve stimulation, numerous lymphocytes, predominantly CD4+ T cells, and monocytes were recruited in the airways of infected rats, whereas no difference was found in pathogen-free controls. RSV induced overexpression of the neurokinin 1 (NK1) receptor for substance P on discrete lymphocyte subpopulations within the bronchial-associated lymphoid tissue (BALT), and treatment with a specific NK1 receptor antagonist abolished the recruitment of both lymphocytes and monocytes to infected airways. Our data suggest that airborne irritants stimulating mucosal sensory fibers during RSV infection exert important immunomodulatory effects by attracting to the infected airways selected lymphocyte subpopulations from the local BALT as well as monocytes.

Apnea is a common complication of respiratory syncytial virus (RSV) infection in young infants. The purpose of this study was to determine whether this infection affects apnea triggered by sensorineural stimulation in weanling rats. We also studied which neurotransmitters are involved in this response and whether passive prophylaxis with a specific neutralizing antibody (palivizumab) confers protection against it. Weanling rats were inoculated intranasally with RSV, adenovirus, or virus-free medium. Changes in respiratory rate and apnea in response to nerve stimulation with increasing doses of capsaicin were measured by plethysmography. Capsaicin-induced apnea was significantly longer in RSV-infected rats at postinoculation days 2 (upper airways infection) and 5 (lower airways infection), and apnearelated mortality occurred only in the RSV-infected group. Reduction in the duration of apnea was observed after selective inhibition of central ␥-aminobutyric acid (GABA) type A receptors and neurokinin type 1 receptors for substance P. Prophylactic palivizumab protected against apnea and apnea-related mortality. These results suggest that sensorineural stimulation during RSV infection is associated with the development of apnea and apnea-related death in early life, whose mechanism involves the release of GABA acting on central GABA type A receptors and substance P acting on neurokinin type 1 receptors. Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infections in infants and young children and presents a large public health problem worldwide (1). Although most infections have a mild course, RSV can cause severe respiratory compromise, especially in patients with underlying cardiorespiratory conditions, and predisposes to the development of childhood asthma (2). Apnea can be the presenting sign of this infection, and its incidence varies between 16 and 25% of infected infants, with a particularly high risk associated with young age (Ͻ3 mo) and prematurity (3-5). Because of its ability to interfere with ventilatory control, it has been suggested that RSV infection may also be a precipitating factor in cases of sudden infant death (SID) (6-8), yet the pathophysiology of apnea associated with RSV infection remains unclear, and no specific prophylaxis or treatment is currently available to protect infants from this complication.Among the factors that influence airway function are neural control mechanisms, which can undergo dysregulation during and after viral respiratory infections (9). In particular, the local irritation of C-type nociceptive afferents in infected airways evokes bronchospasm, neurogenic inflammatory edema, and recruitment and activation of leukocytes (10). We showed previously that RSV infection amplifies the inflammatory and immunomodulatory effects of sensory nerves via both presynaptic (increased synthesis and release of substance P) and postsynaptic [up-regulation of neurokinin 1 (NK 1 ) receptors] mechanisms (11-13), both involving the overexpression of ner...

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