IntroductionProvision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice.MethodsNine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation.ResultsAnti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment.ConclusionsAnti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.
Objective. Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-B activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation. The aim of this study was to assess the efficacy of thalidomide in patients with severe EOS, based on etiology supporting an initial role of NF-B in activation of this disease.Methods. Thalidomide was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. To elucidate the mechanism of the drug, peripheral blood monocytes were isolated from the patients and stimulated with cytokines (macrophage colony-stimulating factor, tumor necrosis factor ␣, and interleukin-4), and their ability to form multinucleated giant cells (MGCs) and osteoclasts was measured.Results. Both patients showed dramatic improvement of their clinical symptoms (alleviation of fever and optic nerve papillitis, achievement of a response according to the American College of Rheumatology Pediatric 50 and Pediatric 70 criteria) and laboratory findings.Monocytes from patients with EOS had a greater ability to survive and induce MGCs and osteoclasts than those from healthy control subjects. The formation of MGCs and osteoclasts was inhibited by the presence of thalidomide. Conclusion. The ability of thalidomide to improve clinical symptoms and laboratory findings in patients with EOS indicates a central role for NF-B activity in this disorder. Inhibition of IKK might be a pharmacologic action by which thalidomide down-regulates NF-B signaling. Thalidomide may be an effective medication in patients with severe complications of EOS, including ocular involvement.Sarcoidosis is a multiorgan inflammatory disease with an unknown etiology, characterized by the histologic features of noncaseating epithelioid granulomas. Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, involves the triad of exanthema, arthritis, and uveitis, along with recurrent fever, without apparent pulmonary involvement (1). The symptoms of EOS are sometimes uncontrolled by corticosteroids, cyclosporine, antimalarials, and/or methotrexate (2). The disease is symptomatically progressive and can have profound complications, such as joint destruction, visceral involvement, and ocular involvement (uveitis and/or retinopathy) with a high probability of blindness (1-3). Severe growth retardation is observed in some patients.EOS is associated with a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 gene (NOD2) that causes accelerated basal NF-B activation (without muramyldipeptide stimulation), which is a genetic etiology it shares with Blau syndrome (4). It has been hypothesized that increased basal NF-B activity is the key t...
Background Although there are many reports on Juvenile Idiopathic arthritis-associated uveitis (JIA-U) from various countries, especially from Europe and North America, there are few reports from Asia. Our aim was to investigate the epidemiology, characteristics and predictors of JIA-U in Japan. Methods Data were retrospectively collected on 726 patients with JIA from medical records as of April 2016 at 15 medical centers specialized in pediatric rheumatic diseases. Of these, patients with uveitis were further investigated for the specific characteristics of this manifestation. Results The prevalence of uveitis was 6.1% in the 726 JIA patients examined. Incidence of uveitis was significantly higher in patients with an earlier arthritis onset (2.6-vs.-5.8 years, P < 0.0001), oligoarthritis (16.1%-vs.-1.6%, P < 0.001), or anti-nuclear antibodies. On the contrary, it was significantly less common in patients with rheumatoid factor or anti-cyclic citrullinated peptide antibodies. A history of using methotrexate (MTX), infliximab or adalimumab was also associated with uveitis occurrence. The median age at uveitis diagnosis was 5 years, and the median time from arthritis onset to uveitis diagnosis was 2 years. The occurrence of anterior and bilateral uveitis was 79.3 and 53.7%, respectively. There were no symptoms at uveitis diagnosis in 58.5% of cases. Complications arising between the time of uveitis diagnosis and the last observation increased from 31.7 to 56.1%; in particular, cataract was increased 3-fold. While no patients lost their vision, 61.9% did not recover normal vision (≥ 1.0), and in many cases active uveitis persisted, especially in males. In addition to steroid eye drops (97.6%) and MTX (15.4%), biological agents were used for treating the uveitis in 41.5% of patients. Conclusions The epidemiology, characteristics and predictors of JIA-U in Japan are described here for the first time. Although the prevalence of JIA-U in Japan is lower than in predominantly Caucasian cohorts, as reported from North America and Europe, the epidemiology, characteristics and predictors were found to be similar.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.