scholarly journals Sa1742 – Interleukin-10 Knockout Mice Do Not Exhibit Persistent Leftsided Colitis: A Natural History Endoscopic Surveillance Study

2019 ◽  
Vol 156 (6) ◽  
pp. S-383
Author(s):  
Jaeho Park ◽  
Seung Young Kim ◽  
Gabriela Leite ◽  
Mark Pimentel ◽  
Ali Rezaie
2021 ◽  
Author(s):  
Seung Young Kim ◽  
Jaeho Park ◽  
Gabriela Leite ◽  
Mark Pimentel ◽  
Ali Rezaie

Background: Interleukin (IL)-10 knockout (KO) mice, used as a model for inflammatory bowel disease (IBD), develop chronic enterocolitis. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models. We aimed to assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies. Methods: BALB/cJ IL10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0-3 points each). An endoscopic score ≥1 point was considered as the presence of colitis/flare. Results: IL-10 KO mice (N=40, 9 female) were assessed. Mean age at first endoscopy was 62.5±2.5 days; average number of procedures per mouse was 6.0±1.3. A total of 238 endoscopies were conducted every 24.8±8.3 days, corresponding to 124.1±45.2 days of surveillance per mouse (13.6 years cumulative surveillance). Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5±1.3 (range: 1-6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2-3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies. Conclusions: In this largest endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.


1999 ◽  
Vol 67 (9) ◽  
pp. 4435-4442 ◽  
Author(s):  
Ching Li ◽  
Inés Corraliza ◽  
Jean Langhorne

ABSTRACT Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/−mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudimalaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced.


2020 ◽  
Vol 18 (7) ◽  
pp. 1626-1635.e7 ◽  
Author(s):  
Mengfei Liu ◽  
Zhen Liu ◽  
Fangfang Liu ◽  
Chuanhai Guo ◽  
Ruiping Xu ◽  
...  

2015 ◽  
Vol 21 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Kristine Holgersen ◽  
Ross Dobie ◽  
Colin Farquharson ◽  
Rob vanʼt Hof ◽  
Syed Faisal Ahmed ◽  
...  

2013 ◽  
Vol 108 ◽  
pp. S510
Author(s):  
Joanna Lopez ◽  
Gauree Konijeti ◽  
Deanna Nguyen ◽  
Jenny Sauk ◽  
Vijay Yajnik ◽  
...  

2003 ◽  
Vol 9 (1-2) ◽  
pp. 10-17 ◽  
Author(s):  
Giuseppina Caligiuri ◽  
Mats Rudling ◽  
Véronique Ollivier ◽  
Marie-Paule Jacob ◽  
Jean-Baptiste Michel ◽  
...  

2000 ◽  
Vol 68 (4) ◽  
pp. 2142-2147 ◽  
Author(s):  
H. Yu ◽  
S. Z. Nasr ◽  
V. Deretic

ABSTRACT Cystic fibrosis (CF) is characterized by dysfunction of the digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections. Chronic lung infections withPseudomonas aeruginosa, intense neutrophil-dominated airway inflammation, and progressive lung disease are the major cause of high morbidity and mortality in CF. Here we investigated the effects of malnutrition in CF on innate lung defenses, susceptibility to P. aeruginosa colonization, and associated inflammation, using aerosol models of acute and chronic infections in normal, malnourished, and transgenic mice. CFTRm1Unc−/− knockout mice displayed body weight variations and showed variable pulmonary clearance of P. aeruginosa. This variability was not detected in bitransgenicCFTRm1Unc−/− (FABP-hCFTR) mice in which the intestinal defect had been corrected. Diet-induced protein calorie malnutrition in C57BL/6J mice resulted in impaired pulmonary clearance of P. aeruginosa. Tumor necrosis factor alpha (TNF-α) and nitrite levels detected upon exposure to P. aeruginosaaerosols were lower in the lungs of the malnourished C57BL/6J mice relative than in lungs of mice fed a normal diet. The role of TNF-α and reactive nitrogen intermediates in P. aeruginosaclearance was tested in TNF-α and inducible nitric oxide synthase (iNOS) knockout mice. P. aeruginosa clearance was diminished in transgenic TNF-α- and iNOS-deficient mice. In contrast to the effects of TNF-α and iNOS, gamma interferon knockout mice retained a full capacity to eliminate P. aeruginosafrom the lung. Malnutrition also contributed to excessive inflammation in C57BL/6J mice upon chronic challenge with P. aeruginosa. The repeatedly infected malnourished host did not produce interleukin-10, a major anti-inflammatory cytokine absent or diminished in the bronchoalveolar fluids of CF patients. These results are consistent with a model in which defective CFTR in the intestinal tract leads to nutritional deficiency which in turn contributes to compromised innate lung defenses, bacterial colonization, and excessive inflammation in the CF respiratory tract.


2014 ◽  
Vol 21 (1) ◽  
pp. 137-147 ◽  
Author(s):  
Kristine Holgersen ◽  
Peter Helding Kvist ◽  
Axel Kornerup Hansen ◽  
Thomas Lindebo Holm

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