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IL-28 (IFN-λ) cytokines exhibit potent antiviral and antitumor function but their full spectrum of activities remains largely unknown. Recently, IL-28 cytokine family members were found to be profoundly down-regulated in allergic asthma. We now reveal a novel role of IL-28 cytokines in inducing type 1 immunity and protection from allergic airway disease. Treatment of wild-type mice with recombinant or adenovirally expressed IL-28A ameliorated allergic airway disease, suppressed Th2 and Th17 responses and induced IFN-γ. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28Rα−/− mice exacerbated allergic airway inflammation by augmenting Th2 and Th17 responses, and IgE levels. Central to IL-28A immunoregulatory activity was its capacity to modulate lung CD11c+ dendritic cell (DC) function to down-regulate OX40L, up-regulate IL-12p70 and promote Th1 differentiation. Consistently, IL-28A-mediated protection was absent in IFN-γ−/− mice or after IL-12 neutralization and could be adoptively transferred by IL-28A-treated CD11c+ cells. These data demonstrate a critical role of IL-28 cytokines in controlling T cell responses in vivo through the modulation of lung CD11c+ DC function in experimental allergic asthma.

We sought to determine the type of pulmonary involvement in microscopic polyangiitis (MPA), primarily focusing on pulmonary fibrosis (PF), its prevalence, temporal relationship with other disease manifestations and outcome.33 patients (16 males) with biopsy proven perinuclear anti-neutrophilic cytoplasmic antibodypositive MPA (age 63.5 yrs) participated in the study. Pulmonary involvement was assessed using standard methods, including radiographic imaging (chest radiographs and high-resolution computed tomography), pulmonary function testing, bronchoscopy and bronchoalveolar lavage, and, if indicated, lung biopsy. All-cause mortality was analysed by the Kaplan-Meier method and was compared between MPA patients with and without PF.At the time of diagnosis, renal involvement was detected in all patients, with renal biopsies being consistent with segmental necrotising glomerulonephritis in all patients. The most common respiratory symptom was haemoptysis, which was found in nine (27%) patients. PF was present in 12 (36%) patients at the time of diagnosis, whereas one patient developed PF while on therapy ,10 yrs after disease diagnosis. In seven patients with PF, respiratory symptoms related to fibrosis preceded other disease manifestations by a median (range) period of 13 (5-120) months. Patients were followed up for a period of 38¡30 months. Presence of PF was associated with increased mortality (p50.02), with six deaths occurring in the fibrotic group and one in the nonfibrotic group. In the fibrotic group most deaths were related to PF.PF occurs frequently in MPA, may precede other disease manifestations by a variable length of time and has a poor prognosis.

Conclusion. DE-MRI can identify myocardial fibrosis in a significant percentage of patients with SSc and may be a useful noninvasive tool for determining cardiac involvement.

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