Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. Whether these exacerbations result from direct infection of the lower airway or from indirect mechanisms consequent on infection of the upper airway alone is currently unknown. Lower respiratory infection was investigated in vitro by exposing primary human bronchial epithelial cells to rhinoviruses and in vivo after experimental upper respiratory infection of human volunteers. Bronchial infection was confirmed by both approaches. Furthermore, rhinoviruses induced production of interleukin-6, -8, and -16 and RANTES and were cytotoxic to cultured respiratory epithelium. This evidence strongly supports a direct lower respiratory epithelial reaction as the initial event in the induction of rhinovirus-mediated asthma exacerbations. The frequency of infection and the nature of the inflammatory response observed are similar to those of the upper respiratory tract, suggesting that rhinovirus infections may be one of the most important causes of lower in addition to upper respiratory disease.

Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations.

Rhinoviruses are the main cause of the common cold and precipitate the majority of asthma exacerbations. RT-PCR followed by internal probe hybridisation or Southern blotting, or nested PCRs are currently the most sensitive methods for their identification. However, none of the published techniques can differentiate satisfactorily rhinoviruses from other picornaviruses. Examination of the restriction maps of sequenced rhinoviruses, revealed a highly conserved BglI restriction site (GCCnnnnnGGC), located exactly in the middle of the 380-bp amplicon generated with the OL26-OL27 primer pair, which has been used extensively in the past to identify picornaviruses. Such a site was either not present, or positioned differently in other picornaviruses of known sequence. It was, therefore, considered that digestion of rhinovirus amplicons with this enzyme would result in two equal length fragments, generating a single 190-bp band in gel electrophoresis. In contrast, either one undigested 380-bp band or a double-band pattern would appear in amplicons from other picornaviruses. To test this hypothesis, Bgl digestions of OL26-OL27 amplicons from cultured and wild-type rhinoviruses, whose identity was confirmed by acid lability, as well as from echo, polio and coxsackie viruses were carried out. All rhinovirus samples were digested successfully generating single bands. Among the other picornaviruses, only 6.6% presented a single band pattern, while the rest were as predicted from the model. With a sensitivity of 100% and a specificity over 90%, the method described, which is rapid and remarkably easy to perform, can be used to distinguish rhinoviruses from other picornaviruses to a considerable extent.

Background: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. Methods: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. Results: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-α, INF-γ, IL-4, or costimulation with TNF-α and INF-γ CCL24 mRNA was significantly enhanced (3.2–19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-α, INF-γ or IL-4 induced CCL24 protein (0.1–0.3 ng/ml) in epithelial cells. Costimulation with TNF-α and IL-4 (0.1–30 and 1–30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18–0.31 ng/ml). Conclusion: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.