Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis

Turner, 2008, Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy, Gut, 57, 331, 10.1136/gut.2007.136481 Truelove, 1955, Cortisone in ulcerative colitis; final report on a therapeutic trial, Br Med J, 1041, 10.1136/bmj.2.4947.1041 Turner, 2011, Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN, Am J Gastroenterol, 106, 574, 10.1038/ajg.2010.481 Turner, 2007, Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression, Clin Gastroenterol Hepatol, 5, 103, 10.1016/j.cgh.2006.09.033 Sylvester, 2011, Fecal osteoprotegerin may guide the introduction of second-line therapy in hospitalized children with ulcerative colitis, Inflamm Bowel Dis, 17, 1726, 10.1002/ibd.21561 Kabakchiev, 2010, Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis, PLoS One, 5 Turner, 2010, Glucocorticoid bioactivity does not predict response to steroid therapy in severe pediatric ulcerative colitis, Inflamm Bowel Dis, 16, 469, 10.1002/ibd.21070 Turner, 2010, Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response, Gut, 59, 1207, 10.1136/gut.2010.211755 Michail, 2012, Alterations in the gut microbiome of children with severe ulcerative colitis, Inflamm Bowel Dis, 18, 1799, 10.1002/ibd.22860 Turner, 2010, Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response, Gastroenterology, 138, 2282, 10.1053/j.gastro.2010.02.047 Littman, 2010, Th17 and regulatory T cells in mediating and restraining inflammation, Cell, 140, 845, 10.1016/j.cell.2010.02.021 Chikanza, 2003, The molecular and cellular basis of corticosteroid resistance, J Endocrinol, 179, 301, 10.1677/joe.0.1790301 Nishimoto, 2006, Interleukin 6: from bench to bedside, Nat Clin Pract Rheumatol, 2, 619, 10.1038/ncprheum0338 Mudter, 2007, Il-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance, Inflamm Bowel Dis, 13, 1016, 10.1002/ibd.20148 Neurath, 2011, IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer, Cytokine Growth Factor Rev, 22, 83, 10.1016/j.cytogfr.2011.02.003 Sventoraityte, 2008, Immune system alterations in patients with inflammatory bowel disease during remission, Medicina (Kaunas), 44, 27, 10.3390/medicina44010005 Travis, 2011, Predicting the need for colectomy in severe ulcerative colitis: a critical appraisal of clinical parameters and currently available biomarkers, Gut, 60, 3, 10.1136/gut.2010.216895 Turner, 2007, Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study, Gastroenterology, 133, 423, 10.1053/j.gastro.2007.05.029 Seo, 1995, Evaluation of disease activity in patients with moderately active ulcerative colitis: comparisons between a new activity index and Truelove and Witts' classification, Am J Gastroenterol, 90, 1759 Lindgren, 1998, Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis, Eur J Gastroenterol Hepatol, 10, 831, 10.1097/00042737-199810000-00003 Hyams, 2012, Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis, Clin Gastroenterol Hepatol, 10, 391-9, 10.1016/j.cgh.2011.11.026 Ishiguro, 1999, Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis, J Gastroenterol, 34, 66, 10.1007/s005350050218 Raddatz, 2005, Quantitative measurement of cytokine mRNA in inflammatory bowel disease: relation to clinical and endoscopic activity and outcome, Eur J Gastroenterol Hepatol, 17, 547, 10.1097/00042737-200505000-00012 Balding, 2004, Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms, Mediators Inflamm, 13, 181, 10.1080/09511920410001713529 Tsampalieros, 2011, Use of C-reactive protein in children with newly diagnosed inflammatory bowel disease, J Pediatr, 159, 340, 10.1016/j.jpeds.2011.04.028 Strandberg, 2008, Effect of budesonide and formoterol on IL-6 and IL-8 release from primary bronchial epithelial cells, J Asthma, 45, 201, 10.1080/02770900801890372 Quante, 2008, Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1, Am J Respir Cell Mol Biol, 39, 208, 10.1165/rcmb.2007-0014OC Tripathi, 2008, Does cytokine gene polymorphism affect steroid responses in idiopathic nephrotic syndrome?, Indian J Med Sci, 62, 383, 10.4103/0019-5359.44017 Yokota, 2008, Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial, Lancet, 371, 998, 10.1016/S0140-6736(08)60454-7 Lowenberg, 2006, Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN, EMBO Rep, 7, 1023, 10.1038/sj.embor.7400775 Harr, 2009, Glucocorticoid-mediated inhibition of Lck modulates the pattern of T cell receptor-induced calcium signals by down-regulating inositol 1,4,5-trisphosphate receptors, J Biol Chem, 284, 31860, 10.1074/jbc.M109.005579 Hausherr, 2007, Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases, Oncogene, 26, 4987, 10.1038/sj.onc.1210306 Smolinska, 2011, Hck tyrosine kinase regulates TLR4-induced TNF and IL-6 production via AP-1, J Immunol, 187, 6043, 10.4049/jimmunol.1100967 Irusen, 2002, p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma, J Allergy Clin Immunol, 109, 649, 10.1067/mai.2002.122465 Webster, 2001, Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance, Proc Natl Acad Sci USA, 98, 6865, 10.1073/pnas.121455098 Franchimont, 1999, Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor, J Clin Endocrinol Metab, 84, 2834 Hawrylowicz, 2002, A defect in corticosteroid-induced IL-10 production in T lymphocytes from corticosteroid-resistant asthmatic patients, J Allergy Clin Immunol, 109, 369, 10.1067/mai.2002.121455 Kobayashi, 2008, IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease, Gut, 57, 1682, 10.1136/gut.2007.135053 Iwanami, 2008, Crucial role of the interleukin-6/interleukin-17 cytokine axis in the induction of arthritis by glucose-6-phosphate isomerase, Arthritis Rheum, 58, 754, 10.1002/art.23222 Ruddy, 2004, Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members, J Biol Chem, 279, 2559, 10.1074/jbc.M308809200 van den Berg, 2005, Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production to tumor necrosis factor-alpha in structural lung cells, Am J Respir Cell Mol Biol, 33, 97, 10.1165/rcmb.2005-0022OC Levine, 2011, Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification, Inflamm Bowel Dis, 17, 1314, 10.1002/ibd.21493 Turner, 2007, Development and evaluation of a Pediatric Ulcerative Colitis Activity Index (PUCAI): A prospective multicenter study, Gastroenterology, 133, 423, 10.1053/j.gastro.2007.05.029