German shepherd dogs (GSD) are predisposed to enteropathies such as inflammatory bowel disease (IBD) and small intestinal bacterial overgrowth (SIBO). The present study examined the role of cytokines in the immunopathogenesis of both conditions. Duodenal mucosal biopsies were taken from GSDs with small intestinal enteropathies (group 1; N = 16) or control dogs (group 2, N = 12). IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-gamma, TNF-alpha, and TGF-beta1 mRNA expression was determined by semiquantitative reverse transcriptase polymerase chain reaction. IL-2, IL-5, IL-12p40, TNF-alpha, and TGF-beta1 mRNA expression in group 1 dogs was significantly greater than in group 2 dogs (all P<0.01), but there were no significant differences between dogs with IBD or SIBO. Further, antibiotic treatment in five dogs with SIBO, resulted in reduced TNF-alpha and TGF-beta1 mRNA expression (P<0.05). Such alterations in cytokine mRNA expression suggest heightened immune responses within the duodenal mucosa in GSDs with either SIBO or IBD.
"IBD is believed to be the most common cause of chronic gastrointestinal signs in dogs, and although the clinical and histological picture is different from that seen in humans, the molecular pathogenesis is thought to be similar in both diseases. However, so far, no clear cytokine expression profile has been associated with canine IBD (De Majo et al., 2008; German et al., 2000) and – to the authors' knowledge -the relevance of Th17 cells for the disease has not been assessed so far in dogs. Discrepancies in the results of studies investigating cytokines in canine IBD could be due to different techniques used, differences in breeds of dogs included, or sample sizes. "
[Show abstract][Hide abstract] ABSTRACT: Inflammatory bowel disease (IBD) is a common cause of chronic diarrhoea in dogs. In people, specific cytokine patterns attributed to T cell subsets, especially T helper cell [Th]1, Th17 and regulatory T(reg) cells have emerged in IBD. In contrast, no specific involvement of a distinct T cell subset has been described so far in canine IBD. Thus, the aim of the present study was to assess gene expression of signature cytokines in duodenal tissues from 18 German shepherd dogs with IBD (group 1), 33 dogs of other breeds with IBD (group 2) and 15 control dogs (group 3). Relative quantification of IL-17A, IL-22, IL-10, IFNy and TGFβ was performed. Expression of IL-17A was significantly lower in groups 1 and 2 compared to group 3 (p=0.014), but no difference in the expression of IL-22 (p=0.839), IFNγ (p=0.359), IL-10 (p=0.085) or TGFβ (p=0.551) across groups was detected. Thus, no clear evidence for the involvement of Th-17 signature cytokines in canine IBD at the mRNA level could be shown. The contribution of specific T cell subsets to the pathogenesis of canine IBD warrants further investigation.
"Some investigators have recently focused on the effect disturbing the homeostasis between the immune system and luminal antigens in the intestinal microenvironment . Similarly, several reports have evaluated the role of cytokines [6,8,16,23,25], subpopulations of leukocytes [18,26], lymphocyte apoptosis , toll-like receptors , nuclear factor kappa-beta  or intestinal microbial communities . "
[Show abstract][Hide abstract] ABSTRACT: Distended lacteals, described as expanded white villi in duodenum, are strongly indicative of primary intestinal lymphangiectasia. In the present study, we evaluated the significance of white spots present in the duodenal mucosa of dogs with lymphocytic plasmacytic enteritis (LPE). Fifty dogs with LPE were included in this study, and white spots were detected in the duodenal mucosa in 22 dogs during endoscopy. Hypoproteinemia was more frequent in dogs with white spots than in dogs without spots (p = 0.02). Serum protein and albumin concentration were significantly lower in LPE dogs with white spots (p = 0.038) compared to LPE dogs without white spots (p = 0.039). There was a significant correlation between white spots density and lymphatic dilatation histological scores (p = 0.023; ρ = 0.481). These results suggest that the presence of white spots in the duodenal mucosa of dogs is not a finding exclusive for intestinal lymphangiectasia. Low serum protein and albumin concentrations together with lymphatic dilatation seem to be related to the presence of white spots in the duodenal mucosa of LPE dogs.
"Unfortunately only a few antibodies to canine cytokines are available and their utilities have not been fully worked out. Some (German et al., 2000; Ridyard et al., 2002; Cave, 2003; Spichiger et al., 2005), but not all (Peters et al., 2005), researchers have shown alterations in mRNA cytokine levels in canine CE. German et al. (2000) showed increased IL-2, IL-5, IL-12p40, TNF-a, and TGF-beta1 mRNA expression in duodenal mucosal biopsies taken from German shepherd dogs with small intestinal enteropathies. Ridyard et al. (2002) showed that canine lymphocytic–plasmacytic colitis was associated with over-expression of IL-2 and TNF-a mRNA and suggested this was the result of activation of CD4+ T-helper lymphocytes and increased production of T-helper-1-type cytokines. "
[Show abstract][Hide abstract] ABSTRACT: Homeostasis in the intestinal microenvironment between the immune system and luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory cytokines likely play a role in the pathogenesis of intestinal inflammation. Several inflammatory and immunoregulatory genes have associated nuclear factor-kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappaB within treatment groups, and (3) the effect of specific therapy on NF-kappaB activation. Dogs with chronic enteropathy were studied (n=26) and compared with 13 healthy dogs. Ten dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease (IBD). NF-kappaB activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappaB. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of activated NF-kappaB was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappaB were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB positive epithelial cells were observed in FRD dogs compared to IBD dogs (p<0.05). After therapy, the number of macrophages and epithelial cells staining positive for activated NF-kappaB decreased (p<0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappaB is closely associated with the pathophysiology of canine chronic enteropathy. Down-regulation follows successful therapy.
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