Rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H(1)-receptor blockers. Anti-inflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined.|We have investigated the effects of desloratadine and loratadine on rhinovirus-induced ICAM-1 expression, mRNA upregulation, and promoter activation.|Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with desloratadine and loratadine for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated with flow cytometry, and ICAM-1 mRNA was evaluated with specific RT-PCR. In A549 cells promoter activation was evaluated with a chloramphenicol acetyltransferase assay, and binding activity of nuclear factor kappa B in nuclear extracts was evaluated with an electrophoretic mobility shift assay.|Desloratadine and loratadine (0.1-10 micromol/L) inhibited rhinovirus-induced ICAM-1 upregulation in both primary bronchial or transformed (A549) respiratory epithelial cells. In A549 cells the 2 compounds showed a dose-dependent inhibition with similar efficacy (inhibitory concentration of 50%, 1 micromol/L). Desloratadine and loratadine also inhibited ICAM-1 mRNA induction caused by rhinovirus infection in a dose-dependent manner, and they completely inhibited rhinovirus-induced ICAM-1 promoter activation. Desloratadine also inhibited rhinovirus-induced nuclear factor kappa B activation. Desloratadine and loratadine had no direct effect on rhinovirus infectivity and replication in cultured epithelial cells.|These effects are unlikely to be mediated by H(1)-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.

Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention.|To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro.|BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs.|RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1alpha. When RVs were inactivated cytokine up-regulation was almost completely lost.|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.

Levels of circulating interleukin (IL)-2, IL-6, and IL-10, measured by enzyme-linked immunosorbent assay, were significantly higher in patients with cat scratch disease (CSD) than in healthy control subjects; no induction of IL-12 was observed, and levels of interferon-gamma and IL-4 were generally not detectable. This is the first report showing increased circulating cytokine levels in patients with CSD. The induction of these mediators can partly explain some clinical and pathological features of the disease.

Viral respiratory infections have been related to asthma in several ways. It is well established that viral common colds precipitate exacerbations of asthma. Severe bronchiolitis in early life is related to subsequent wheezing and therefore may represent a marker of susceptibility to asthma; alternatively, it could be involved in the initiation of the disease. Finally, it is possible that some infections may protect from the development of asthma and allergies by promoting a type-1 host response. However, whether respiratory or other viruses could mediate such a protective effect is debated. The design and implementation of novel anti- or proviral strategies targeting asthma depends on the resolution of these questions. This review presents current evidence on the epidemiologic correlations and proposed mechanisms for the involvement of viral infections in the development and progression of asthma.

Cat scratch disease (CSD) commonly manifests as regional self-limited lymphadenitis. However, dissemination of the infection to distant multiple sites may occur even in immunocompetent patients. We report a series of 11 children with fever and extralymphocutaneous manifestations of CSD, in order to highlight potential multiorgan involvement in patients with febrile CSD. To be eligible for enrollment, patients had to present with involvement of sites other than regional lymph nodes. The diagnosis was based on suggestive clinical criteria, histological findings and positive serology. The utilization of ultrasound imaging revealed hepatic lesions in 3 children and splenic lesions in 8 children, whereas osteolytic lesions were observed in 4 children by bone scan. Hepatic or splenic involvement was not suggested by clinical signs or biochemical investigation in 2/3 and 6/8 children, respectively. Bone involvement was supported either by relative symptoms or signs. Our findings indicate that, in the presence of fever, extralymphocutaneous manifestations have to be anticipated in patients with clinically suspected CSD. The systematic use of imaging modalities in patients with serologically documented Bartonella henselae infection could contribute to a better understanding of the clinical spectrum of CSD.