ABSTRACT. The yellow nail syndrome, combination of yellow discoloured nails, lymphedema and pleural effusions, is a rare clinical condition. A review of the literature, including 97 patients, is presented. Most patients developed yellow nail syndrome in early middle age, and the overall male: female ratio was 1: 1.6. The etiology of the syndrome is obscure, while the pathogenesis seems to involve impaired lymphatic drainage. A patient, whose recurrent pleural effusions were effectively controlled by chemical pleurodesis, is also presented.

Defensins represents an integral part of the innate immune system serving to ward off potential pathogens and to protect the intestinal barrier from microbial encroachment. In addition to their antimicrobial activities, defensins in general, and human β-defensin 2 (hBD2) in particular, also exhibit immunomodulatory capabilities. In this report, we assessed the therapeutic efficacy of systemically administered recombinant hBD2 to ameliorate intestinal inflammation in three distinct animal models of inflammatory bowel disease; i.e., chemically induced mucosal injury (DSS), loss of mucosal tolerance (TNBS), and T-cell transfer into immunodeficient recipient mice. Treatment efficacy was confirmed in all tested models, where systemically administered hBD2 mitigated inflammation, improved disease activity index, and hindered colitis-induced body weight loss on par with anti-TNF-α and steroids. Treatment of lipopolysaccharide (LPS)-activated human peripheral blood mononuclear cells with rhBD2 confirmed the immunomodulatory capacity in the circulatory compartment. Subsequent analyzes revealed dendritic cells (DCs) as the main target population. Suppression of LPS-induced inflammation was dependent on chemokine receptor 2 (CCR2) expression. Mechanistically, hBD2 engaged with CCR2 on its DC target cell to decrease NF-κB, and increase CREB phosphorylation, hence curbing inflammation. To our knowledge, this is the first study showing in vivo efficacy of a systemically administered defensin in experimental disease.

Overnutrition is the principal cause of insulin resistance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD.

Background: Asthma is an airway inflammatory disease and a major health problem worldwide. Anti-inflammatory steroids and bronchodilators are the gold-standard therapy for asthma. However, they do not prevent the development of the disease, and critically, a subset of asthmatics are resistant to steroid therapy. Objective: To elucidate the therapeutic potential of human β-defensins (hBD), such as hBD2 mild to moderate and severe asthma. Methods: We investigated the role of hBD2 in a steroid-sensitive, house dust miteinduced allergic airways disease (AAD) model and a steroid-insensitive model combining ovalbumin-induced AAD with C muridarum (Cmu) respiratory infection. Results: In both models, we demonstrated that therapeutic intranasal application of hBD2 significantly reduced the influx of inflammatory cells into the bronchoalveolar lavage fluid. Furthermore, key type 2 asthma-related cytokines IL-9 and IL-13, as well as additional immunomodulating cytokines, were significantly decreased after administration of hBD2 in the steroid-sensitive model. The suppression of inflammation was associated with improvements in airway physiology and treatment also suppressed airway hyper-responsiveness (AHR) in terms of airway resistance and compliance to methacholine challenge. Conclusions and Clinical relevance: These data indicate that hBD2 reduces the hallmark features and has potential as a new therapeutic agent in allergic and especially steroid-resistant asthma.