CpG Immunotherapy in Chenopodium album sensitized mice: The comparison of IFN-gamma, IL-10 and IgE responses in intranasal and subcutaneous administrations

<p>Abstract</p> <p>Background</p> <p>Mucosal-based immunotherapy has been already used as an alternative form of allergen delivery. In asthma, the poor success rate of immune modulation could be a consequence of inadequate immune modulation in the airways. Previously, we have found that subcutaneous (S.C) co-administration of a homemade allergenic extract from Chenopodium album (Ch.a) pollen and Guanine-Cytosine containing deoxynucleotides (CpG-ODNs) is effective to prevent the inflammatory responses in mouse. In this study we used CpG/Ch.a for immunotherapy of Ch.a-induced asthma and compared the intranasal (I.N) and S.C routes of administration concerning IFN-γ, IL-10 and total IgE responses.</p> <p>Methods</p> <p>Ch.a sensitized mice were treated intranasaly or subcutaneously using CpG and Ch.a. extract. IFN-γ, IL-10 and total IgE were measured in supernatant culture of splenocytes and bronchoalveolor lavage (BAL) fluids by ELISA. Student's t test was used in the analysis of the results obtained from the test and control mice.</p> <p>Results</p> <p>We found that I.N administration of CpG/Ch.a in sensitized mice significantly increased the production of systemic and mucosal IFN-γ and IL-10 compared to phosphate buffered saline (PBS), Ch.a alone and control ODNs treated sensitized mice (P ≤ 0.001). On the other hand, S.C. route induced the systemic and mucosal IFN-γ in the lower levels than in I.N one, and failed to increase systemic IL-10 induction (P = 0.06). Total serum IgE in CpG/Ch.a treated mice in both routes showed significant decreases compared to three control groups (P ≤ 0.01). The amounts of IgE in BAL fluids were not measurable in all groups.</p> <p>Conclusion</p> <p>According to the results of this experiment we concluded that immunotherapy via the I.N co-administration of CpG/Ch.a in comparison with S.C route is more effective to stimulate the mucosal and regulatory responses in Ch.a induced asthma.</p

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Suppression of airway inflammation by a natural acute infection of the intestinal epithelium

Although chronic intestinal helminth infections may suppress allergen-induced airway pathology by inducing a combination of modified T-helper (Th) 2 and immunosuppressive cytokines, a similar capacity of natural acute intestinal infections has remained untested, despite their global prevalence. Here, we show that allergic airway phenotypes including eosinophilia, eotaxin mRNA, and Th2 cytokines are significantly suppressed in animals that were infected by and that have cleared the intestinal parasite Eimeria vermiformis. Unlike in helminth-infected animals, regulation requires temporal coincidence of infection with sensitization; depends on interferon-γ; and is not associated with an enhanced antigen-specific immunoglobulin G1 response. Moreover, regulation was effective following allergen sensitization in different anatomical sites, and in young and adult mice. These data highlight a transient anatomical dissemination of "functional immunologic dominance" following infection of the gut mucosa. They strongly support the hypothesis that airway allergies are naturally suppressed by both acute and chronic mucosal pathogens, but by different mechanisms