Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells.

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells.     

Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions

Nasal provocation tests with normal saline and methacholine (MC) were performed in 25 atopic and 27 nonatopic subjects in an effort to assess the sources of protein in induced airway secretions. Nasal lavages obtained at baseline and after provocation were analyzed for albumin, total protein, secretory IgA (sIgA), and total IgA. Compared with baseline levels or saline provocation, MC provocation increased the secretion of albumin (p less than 0.025), total protein (p less than 0.001), sIgA (p less than 0.025), and total IgA (p less than 0.025), but did not significantly affect the relative proportions of albumin-to-total protein (albumin percent) or sIgA-to-total IgA (sIgA/total IgA ratio). Nasal pretreatment with atropine significantly inhibited MC-induced secretion of all 4 proteins, again without affecting the albumin percent or the sIgA/total IgA ratio. Because MC is known to stimulate atropine-inhibitable secretion of glandular products, these data suggest that sIgA and albumin may accompany glandular secretions. Immunohistochemical analyses of nasal turbinates confirmed that secretory component was found only on serous cells within submucous glands. Thus, it appears that cholinergic stimulation may regulate sIgA secretion and thereby participate in local nasal (and possibly respiratory tract) immunity.     

A tender sinus does not always mean rhinosinusitis.

BACKGROUND: Sinus tenderness has not been quantitatively assessed. OBJECTIVE: We sought to compare sinus and systemic tenderness in rhinosinusitis, allergic rhinitis, and chronic fatigue syndrome (CFS), and healthy (non-CFS) groups. METHODS: Cutaneous pressures (kg/cm(2)) causing pain at 5 sinus and 18 systemic sites were measured in acute and chronic rhinosinusitis, active allergic rhinitis, healthy non-CFS/no rhinosinusitis, and CFS subjects. RESULTS: Sinus thresholds differed significantly (P 相似文献   

Persistent nonallergic rhinosinusitis

Nonallergic rhinitis is a complex of syndromes that are united by the absence of atopic, TH2 lymphocyte, immunoglobulin E (IgE)-mediated mechanisms. We propose a classification system based on the presence or absence of inflammatory granulocytes. Eosinophilic nonallergic rhinosinusitis may also be called chronic eosinophilic sinusitis syndromes (CESS) to help classify these disorders in which diverse mechanisms of eosinophil chemoattraction and survival predominate. Allergic fungal sinusitis, eosinophilic nasal polyps, aspirin sensitivity, and related disorders would fit in this category. Accumulation of neutrophils occurs in chronic infectious rhinosinusitis, foreign body reactions, and immunodeficiencies. More complex and variable combinations of leukocytes are found in Wegner’s granulomatosis and related syndromes, and during the evolution of viral infections. The noninflammatory disorders can be divided by mechanism into hormonal; sympathetic dysfunction (including antihypertensive adrenergic drug therapy); cholinergic rhinitis; and nociceptive syndromes with hyperalgesia and other features (eg, the nonallergic rhinitis of chronic fatigue syndrome). Therapy based on the most likely pathophysiologic mechanism is anticipated to have the most success, but requires acceptance of the wide differential diagnosis of nonallergic rhinitis and rejection of the obsolete term of “vasomotor rhinitis.”     

The Sinus Headache Explained

The concept of a sinus headache is problematic from neurology, allergology, and rhinology perspectives. It may be considered the final neurological diagnosis of exclusion when criteria for other craniofacial pain syndromes are not met. The International Headache Society definition implicates the presence of acute sinusitis, but this requirement is often not met in practice or with a patient’s perception of the term. Otorhinolaryngologists have a similar exasperation with this cephalgia but tend to attribute idiopathic, nonallergic rhinopathy as the cause. Allergists often see patients who claim to have a sinus headache but instead have perennial allergic rhinitis or nonallergic rhinitis. A fresh perspective is required to determine the characteristics, differential diagnosis, and veracity of the sinus headache. We recommend using the term with caution only if the clinical picture meets the criteria for acute sinusitis–induced headache.     

Pathophysiology of rhinitis. Lactoferrin and lysozyme in nasal secretions.

The antimicrobial proteins lactoferrin (Lf) and lysozyme (Ly) are invariably found in nasal secretions. To investigate the cellular sources and the secretory control of these nasal proteins in vivo, 34 adult subjects underwent nasal provocation tests with methacholine (MC), histamine (H), and gustatory stimuli. Nasal lavages were collected and analyzed for total protein (TP), albumin (Alb), Lf, and Ly. MC (25 mg), H (1 mg), and gustatory stimuli (spicy foods) all increased the concentrations of TP, Alb, Lf, and Ly. However, when each protein was assessed as a percentage of TP (i.e., Alb% = Alb/TP; Lf% = Lf/TP; Ly% = Ly/TP), MC and gustatory stimuli, which both induce glandular secretion, selectively augmented Lf% and Ly% without changing Alb%, while H, which primarily increases vascular permeability, increased Alb% without significantly affecting Lf% or Ly%. Gel electrophoresis and immunoblotting analysis of nasal secretions demonstrated both Lf and Ly in cholinergically induced secretions. Furthermore, histochemical analyses of nasal turbinate tissue revealed Lf and Ly colocalization within the serous cells of submucosal glands, providing evidence that both proteins are strictly glandular products within the nasal mucosa. Therefore, both Lf and Ly are produced and secreted from the glands, and their secretion may be pharmacologically regulated in attempts to improve host defenses.     

Sensing the air around us: The voltage-gated-like ion channel family

Ion channels are a complex set of proteins having many important physiologic and potentially pathologic roles. The flow of ions through these channels and the subsequent cellular depolarization can trigger complex mechanisms such as cardiac rhythm, hormone secretion, and numerous sensory experiences. The transient receptor potential (TRP) channels are an important means for multiple organ systems to interact with their environment. The various TRP channel subfamilies respond to voltage or to ligands such as G-protein coupled receptors. Their ability to sense temperature, pain, stretch, and osmolarity among others enables them to mediate responses such as smooth muscle contraction, cough, or sensation of pain.