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| 1 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC 'responders'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 2 | Tools used to measure airway remodelling in research显示文摘 | Bergeron C Tulic MK Hamid Q | 2007 | Eur Respir J2007，29，10： | 1 |
| 3 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-ind,ucible protein 10 expression in asthmatic airway mucosa显示文摘 | Fukakusa M Bergeron C Tulic MK | 2005 | Allergy Clin Immunol2005，115，2： | 1 |
| 4 | Airway remodelling in asthma: frombenchside to clinical practice显示文摘 | Bergeron C Tulic M K Hamid Q | 2010 | Can Respir J2010，17，4： | 1 |
| 5 | Tools used to measure airway remodeling in resesrch 显示文摘 | Bergeron C Tulic MK Hamid Q | 2007 | Eur Respir J2007，29，3： | 1 |
| 6 | Tools used to measure airway remodelling in research 显示文摘 | Bergeron C Tulic MK Hamid Q | 2007 | Eur Respir J2007，29，3： | 1 |
| 7 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil,IL-8,and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa显示文摘 | FUKAKUSA M BERGERON C TULIC MK | 2005 | J Allergy Clin Immunol2005，115，2： | 1 |
| 8 | Results of application of orthotopic urine diversion according to Studer显示文摘 | Acimovic M Tulic C Dzamic Z | 2007 | Acta Chir Iugosl2007，54，4： | 1 |
| 9 | Oral corti- costeroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa显示文摘 | FUKAKUSA M BERGERON C TULIC MK et ol | 2005 | J Allergy Clin Immunol2005，115，2： | 1 |
| 10 | Airway remodelling in asthma: from benehside to clinical practice显示文摘 | Bergeron C Tulic M K Hamid Q | 2010 | Can Respir J2010，17，4： | 1 |
| 11 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil,IL-8,and IFN-γ-inducible protein-10 expression in asthmatic airway mucosa显示文摘 | Fukakusa M Bergeron C Tulic MK | 2005 | J Allergy Clin Immunol2005，115，2： | 1 |
| 12 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrephil, IL- 8, and IFN-γ- inducible protein -10 expression in asthmatic airway mucosa 显示文摘 | Fukakusa M Bergeron C Tulic MK | 2005 | Allergy Clin lmmunol2005，115，2： | 1 |
| 13 | Polymorphisms mediate impaired responses to respiratory syncytial virus and lipopolysaccharide 显示文摘 | Tulic M K Hurrelbrink R J Prele C M | 2007 | J Immunol2007，179，1： | 1 |
| 14 | Oral corticosteroids decrease eoainophil and CC chemokine expression but increase neutrophil,IL-2,and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa显示文摘 | Fukaktusa M Bergeron C Tulic MK | 2005 | Allergy Clin Immunol2005，115，2： | 1 |
| 15 | Oral corticosterolds decrease eosinophll and CC chemoklne expression but increase neutrophil, IL-8, and IFN-gamma-inducible protein 10 expression in asthmatic airway mucosa显示文摘 | FUKAKUSA M BERGERON C TULIC M K | 2005 | J Allergy Clin Immumol2005，115，2： | 1 |
| 16 | Airway remodelling in asthma: from benchside to clinical practice 显示文摘 | Bergeron C Tulic MK Hamid Q | 2010 | Can Respir J2010，17，4： | 1 |
| 17 | Airway remodelling in asthma:from benchside to clinical practice显示文摘 | Bergeron C Tulic MK Hamid Q | | 0，，： | 1 |
| 18 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil,IL-8, and IFN-γ-inducible protein-10 expression in asthmaric airway mucosa 显示文摘 | Fukakusa M Bergeron C Tulic MK | 2005 | J Allergy Clin Immunol2005，115，： | 1 |
| 19 | Airway remodeling in asthma:from benchside to clinical practice 显示文摘 | Bergeron C Tulic M K Hamid Q | 2010 | Can Respir J2010，17，4： | 1 |
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