The Presence of Rhinovirus in Lower Airways of Patients with Bronchial Asthma

Background: Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients’ peripheral blood mononuclear cells (PBMCs) to RV exposure. Methods: PBMCs obtained from 3 different age groups (2–6 years: young-children group; 7–19 years: youth group; ≧20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA. Results: When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze. Conclusions: These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients’ PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peripheral Blood Mononuclear Cells from Patients with Bronchial Asthma Show Impaired Innate Immune Responses to Rhinovirus in vitro

Iikura

Katsunuma

Saika

et al. 2011

“…A recent report found that, with the sensitive indirect in situ RT-PCR method, rhinoviruses were detected in the mucosal biopsies of 73% of patients with asthma and 22% of nonasthmatic control subjects. Subjects positive for rhinovirus had lower pulmonary function, higher numbers of blood eosinophils and leukocytes, and eosinophilic infiltration in bronchial mucosa [16]. Further evidence suggests a role of deficient IFN-γ [17], IFN-β [18], and type III IFN-λ [19] production in rhinovirus-induced asthma exacerbation and indicates novel mechanisms for the increased susceptibility of subjects with asthma to rhinovirus infection [19,20].…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Corticosteroids on Serum Eosinophil Cationic Protein and Cytokine Production in Rhinovirus- and Respiratory Syncytial Virus-Induced Acute Exacerbation of Childhood Asthma

Katô

Yamada²,

Maruyama³

et al. 2011

Background: Little information is available on eosinophil activation and the cytokine profile in virus-induced acute exacerbation of bronchial asthma; therefore, we examined the effects of treatments that included systemic corticosteroids on serum eosinophil cationic protein (ECP) and 17 cytokines/chemokines in rhinovirus- and respiratory syncytial (RS) virus-induced acute exacerbation of childhood asthma. Methods: We measured the peripheral eosinophil count, as well as the serum levels of ECP and 17 types of cytokines/chemokines (IL-1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17 and IFN-γ, TNF-α, GM-CSF, G-CSF, MCP-1, and MIP-1β), using a multiplex bead-based assay in 21 cases of rhinovirus- and 12 cases of RS virus-induced acute exacerbation of childhood asthma and 13 controls. We also compared the clinical data and the effects of systemic corticosteroids on these responses between rhinovirus and RS virus groups. Results: The serum levels of ECP, IL-5, and IL-6 were significantly elevated in patients with rhinovirus-induced acute exacerbation of asthma compared with controls, while serum IL-1β and IFN-γ were significantly lower in patients with rhinovirus-induced acute exacerbation of asthma than in controls. On the other hand, in RS virus-induced acute exacerbation of asthma, only the peripheral eosinophil count was significantly decreased compared with that in rhinovirus-induced acute exacerbation of asthma and controls. Furthermore, the serum levels of ECP, IL-5, and IL-6 in rhinovirus-induced acute exacerbation of asthma and levels of G-CSF in RS virus-induced acute exacerbation of asthma were significantly reduced after treatments that included systemic corticosteroids, respectively. Conclusion: These results suggest that the effects of systemic corticosteroids on serum ECP and the cytokine profile are different between rhinovirus- and RS virus-induced acute exacerbation of childhood asthma.

“…However, possible causes may be viral infection and aeroallergen [14, 25, 26]. Wos et al [27] recently reported that human rhinovirus is significantly more frequently detected in the lower airway tissue of patients with asthma than in nonasthmatic subjects, and its presence is associated with clinical features of more severe disease. This finding suggests that rhinovirus persistence in the airways of asthmatics may contribute to the development of severe asthma.…”

Section: Discussionmentioning

confidence: 99%

Neutrophilic Inflammation and CXC Chemokines in Patients with Refractory Asthma

Kikuchi

Takaku

et al. 2009

Background: There is evidence that eosinophils and neutrophils are simultaneously increased in the airways of some patients with chronic refractory asthma. The mechanisms by which neutrophils accumulate in the airways of asthmatics remain to be elucidated, however, chemoattractants for neutrophils such as CXC chemokines may affect either the accumulation or functional status of neutrophils in such patients. The objective of the present study was to identify the CXC chemokine responsible for the neutrophilic and possibly eosinophilic inflammation observed in the airways of patients with refractory asthma. Methods: Following the inhalation of hypertonic saline, induced sputum was obtained from 14 healthy controls, 16 patients with mild well-controlled nonrefractory asthma, and 14 patients with refractory asthma. Concentrations of CXC chemokines and differential inflammatory cell counts were determined. Results: The percentages of induced sputum eosinophils were significantly higher both in patients with nonrefractory asthma and in patients with refractory asthma. On the other hand, the percentages of neutrophils were increased only in sputum from patients with refractory asthma. The concentration of IL-8, but not ENA-78 or GRO-α, was also significantly increased in induced sputum from patients with refractory asthma. The concentration of IL-8 correlated significantly with the percentages of neutrophils. Conclusions: The results of the present study suggest that IL-8, but not ENA-78 or GRO-α, may contribute to the observation of neutrophilic inflammation in patients with refractory asthma.