IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema.

BACKGROUND: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL-17C is an epithelial-derived cytokine, whose impact on skin inflammation is unclear. OBJECTIVE: We sought to characterize the role of IL-17C in human ISD. METHODS: IL-17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT-PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL-17C was depleted using a new IL-17C-specific antibody (MOR106) in murine models of psoriasis (IL-23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. RESULTS: Expression of IL-17C mRNA and protein was elevated in various ISD. We demonstrate that IL-17C potentiates the expression of innate cytokines, antimicrobial peptides (IL-36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL-17C in keratinocytes. Cell-free supernatant of keratinocytes stimulated with IL-17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL-17C in immune cell recruitment. IL-17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. CONCLUSION: IL-17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.

Complications of umbilical hernias in horses: 13 cases (1972-1986).

Of 147 horses treated for umbilical hernias over a 13.5-year period, 13 horses (8.8%) developed complications in association with umbilical defects. Six horses had intestinal incarceration; the incarceration was reduced manually in 3 horses before admission, resolved without treatment in 2 others, and was surgically reduced in one. Herniorrhaphy was performed on 4 of the 5 horses in which the incarceration did not require surgical reduction, and the fifth was managed conservatively. A horse with a parietal hernia and a horse with intestinal stragulation were treated surgically; in the latter, the involved intestine was resected. These 8 horses recovered. Three horses developed an umbilical abscess and 2 developed an enterocutaneous fistula through their umbilical hernias. Four of these horses responded well to surgery, but one horse with an enterocutaneous fistula died from electrolyte imbalances and peritonitis after an unsuccessful attempt at simple closure. The results of this study confirmed that complications of umbilical hernias are rare in horses; however, when they do develop, they may be one of various forms, some of which are insidious in onset.