scholarly journals Celiac Disease in Children, Particularly with Accompanying Type 1 Diabetes, Is Characterized by Substantial Changes in the Blood Cytokine Balance, Which May Reflect Inflammatory Processes in the Small Intestinal Mucosa

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Tamara Vorobjova ◽  
Aili Tagoma ◽  
Astrid Oras ◽  
Kristi Alnek ◽  
Kalle Kisand ◽  
...  

Cytokines play a pivotal role in the maintenance of intestinal homeostasis inducing pro- or anti-inflammatory response and mucosal barrier function in celiac disease (CD) and type 1 diabetes (T1D). We aimed to compare the levels of pro- and anti-inflammatory cytokines in CD patients without and with coexisting T1D, as well as to evaluate its association with the presence of enteroviruses (EV), regulatory T cells (Tregs), and dendritic cells (DCs) in small bowel mucosa. Altogether, 72 patients (median age 10.1 years) who had undergone small bowel biopsy were studied. The study group consisted of 24 patients with CD (median age 6.5 years), 9 patients with CD and concomitant T1D (median age 7.0 years), two patients with T1D (median age 8.5 years), and 37 patients (median age 14.0 years) with functional gastrointestinal disorders (FGD) and a normal small bowel mucosa as controls. The levels of 33 cytokines in serum were measured by multiple analysis using the Milliplex® MAP Magnetic Bead assay. The densities of FOXP3+ Tregs, CD11c+ DC, indoleamine 2,3-dioxygenase+ (IDO+) DC, langerin+ (CD207+) DCs, and EV were evaluated by immunohistochemistry as described in our previous studies. Circulating anti-EV IgA and IgG were evaluated using ELISA. The most important finding of the study is the significant increase of the serum levels of IL-5, IL-8, IL-13, IL-15, IL-17F, IL-22, IL-27, IP-10, MIP-1β, sIL-2Rα, sTNFRII, and TNFαin CD patients compared to controls and its correlation with the degree of small bowel mucosa damage graded according to the Marsh classification. The leptin level was higher in females in all study groups. The levels of IL-2, IL-6, IL-12 (P70), IL-15, IP-10, and IFNγcorrelated significantly with the density of FOXP3+ Tregs inlamina propriaof the small bowel mucosa, which supports the evidence about the signaling role of these cytokines in the peripheral maintenance of FOXP3+ Tregs. At the same time, a significant negative correlation occurred between the level of IL-4 and density of FOXP3+ Tregs in controls. Another important finding of our study was the correlation of IL-17F, IP-10, sTNFRII, MCP-1, and GM-CSF with the density of EV-positive cells in thelamina propriaof the small bowel mucosa. Correlation of MIP-1 (CCL-4) with CD103+ DC and langerin+ DC densities may point to their significance in the recruitment of immune cells into thelamina propriaand in driving the inflammatory response in CD patients. Our results suggest the predominance of Th1 and Th17 immune responses over EV VP1 protein in CD and T1D patients. The significant elevation of Th2 cytokines, like IL-5 and IL-13, but not IL-4, in CD patients and its correlation with the degree of small bowel mucosa damage could reflect the role of these cytokines in gut defense and inflammation.

2001 ◽  
Vol 33 ◽  
pp. A66 ◽  
Author(s):  
M. Secondulfo ◽  
D. Iafusco ◽  
L. deMagistris ◽  
A. Sapone ◽  
R. Fiandra ◽  
...  

Nutrients ◽  
2015 ◽  
Vol 7 (9) ◽  
pp. 7143-7162 ◽  
Author(s):  
Gloria Serena ◽  
Stephanie Camhi ◽  
Craig Sturgeon ◽  
Shu Yan ◽  
Alessio Fasano

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Sara N Vallerie ◽  
Farah Kramer ◽  
Jenny E Kanter ◽  
Shelley Barnhart ◽  
Richard M Breyer ◽  
...  

Diabetes is associated with an increased risk of cardiovascular disease, largely due to increased atherosclerosis. Our studies have suggested myeloid cell prostaglandin E 2 (PGE 2 ) production as a possible mediator of diabetes-accelerated atherosclerosis in a virally-induced mouse model of type 1 diabetes. Prostaglandin E Receptor 4 (EP4; Ptger4 ) is a major PGE 2 receptor in myeloid cells. We hypothesized that generation of a mouse model of myeloid cell-targeted EP4-deficiency would allow us to test the role of myeloid EP4 in diabetes-accelerated atherosclerosis. Thus, we generated a Ptger4 flox/flox LysM-Cre tg/tg mouse model. Peritoneal macrophages isolated from these myeloid cell EP4-deficient (EP4 M-/- ) mice expressed <90% Ptger4 mRNA compared to LysM-Cre tg/tg controls (n=10; p<0.0001). To analyze the role of myeloid cell EP4 in diabetes-accelerated atherosclerosis, we transplanted bone marrow from EP4 M-/- mice and littermate controls into lethally irradiated Ldlr -/- RIP-LCMV mice (the model of type 1 diabetes) and, after 7 weeks of recovery, induced diabetes by viral infection and fed the mice a low-fat semi-purified diet for an additional 12 weeks. Diabetic EP4 M-/- mice had similar blood glucose (568 ± 15 vs. 569 ± 15 mg/dl), blood cholesterol (531 ± 29 vs. 510 ± 37 mg/dl), and plasma triglycerides (249 ± 49 vs. 247 ± 44 mg/dl) as diabetic controls (n=15 all groups; mean ± SEM). At the endpoint, aortas were harvested for lesion area quantification. Diabetic EP4 M-/- and diabetic wild type mice had similar lesion area (1.9% ± 0.2 vs. 1.7% ± 0.2), which were both increased (p < 0.01; n=9-15) as compared to their non-diabetic controls. Additionally, we analyzed the role of EP4 in inflammatory activation of myeloid cells ex vivo. EP4-deficiency had no significant effect on basal or lipopolysaccharide (LPS)-induced inflammatory gene expression in the absence of PGE 2 . Pretreatment of the cells with PGE 2 (10 nM) followed by LPS stimulation resulted in a significant reduction of Tnfa and Il6 mRNA compared to LPS alone, and this anti-inflammatory effect of PGE 2 was completely blocked in EP4-deficient cells. These results suggest that myeloid cell EP4 mediates anti-inflammatory actions of PGE 2 but that it is not involved in diabetes-accelerated atherosclerosis.


2016 ◽  
Vol 11 (2) ◽  
Author(s):  
Leonid Klimov ◽  
Marina Stoyan ◽  
Victoria Kuryaninova ◽  
Vyacheslav Kashnikov ◽  
Valentina Botasheva ◽  
...  

1984 ◽  
Vol 58 (4) ◽  
pp. 313-320 ◽  
Author(s):  
S. M. Carroll ◽  
T. A. Robertson ◽  
J. M. Papadimitriou ◽  
D. I. Grove

ABSTRACTThe host-parasite interaction at the site of attachment of the adult hookworm,Ancylostoma ceylanicum, to the small bowel mucosa of the dog has been examined by transmission electron microscopy. The lamina propria around the heads of the worms showed intense infiltration with neutrophilic and cosinophilic leucocytes, and plasma cells were also prominent. Erythrocytcs were cxtravasatcd within the lamina propria while the portions of mucosa engulfed into the buccal cavities of the worms were nccrotic and included aggregates of collagen fibres. Within the lumina of the worms were erythrocytcs in varying stages of lysis together with other nccrotic debris.The mucous membrane adjacent to the heads of the worms was ulcerated while more distant cntcrocytcs were small, distorted and displayed various degrees of microvillar loss. Many mucosal blood vessels had platelet aggregates within their iumina but no fibrin deposition was observed. Vessels were often seen in the bases of the ulcers and were prone to rupture. Erythrocytcs and leucocytes were seen in the dog intestinal lumen in close proximity to the bodies of the worms.


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