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The effects of IL-8, IL- 6 and IL-1 on the risk of celiac disease: a bayesian regression analysis

Maryam Naserinejad, Sadjad Shojaee, Mehdi Ghobakhlou, Elena Lak, Pegah Eslami, Mohamad Amin Pourhoseingholi




Aim: Present study aimed to evaluate association between serum levels of interleukin (IL)-1, IL-6, IL-8, IL-15 genes and interferon (IFN)-? and the risk of celiac disease (CD).

Background: The role of serum cytokine levels in the pathophysiology of CD is still an open field to be explored.

Methods: This case-control study was performed on 110 patients with CD and 46 healthy controls referred to Taleghani Hospital, Tehran, Iran. Expression levels of IL-1, IL-6, IL-8, IL-15 and IFN-? were assessed by enzyme-linked immunosorbent assay (ELISA) kits.

Results: The Bayesian intervention odds ratio (OR) and Highest Posterior Density (HPD) interval were 1.133 (95% credible interval 1.018- 1.269), 0.947 (95% credible interval 0.898 - 0.996) and 1.004 (95% credible interval 1.001- 1.009) for IL-1, IL-6, and IL-8 respectively.

Conclusion: Serum levels of IL-15 and IFN-? have no effect on the risk of CD and its symptoms, but given the OR and the HPD interval obtained for serum levels of IL-1, IL-6 and IL-8, one unit increase in IL-1 serum, the risk of CD 1.13 times more likely and one unit increase in IL-6 serum reduces risk of CD by 15% and about IL-8, the risk of CD increases 0.004 times with a unit increase in IL-8 serum.


Celiac disease, Cytokines, Bayesian Logistic regression model


Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, et al. The Oslo definitions for coeliac disease and related terms. Gut 2013;62:43-52.

Rostami Nejad M, Hogg-Kollars S, Ishaq S, Rostami K. Subclinical celiac disease and gluten sensitivity. Gastroenterol Hepatol Bed Bench 2011;4:102-8.

Shannahan S, Leffler DA. Diagnosis and Updates in Celiac Disease. Gastrointest Endosc Clin N Am 2017;27:79-92.

Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clinical Gastroenterology and Hepatology 2018;16:823-36. e2.

Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Archives of internal medicine 2003;163:286-92.

Ashtari S, Pourhoseingholi MA, Rostami K, Aghdaei HA, Rostami-Nejad M, Busani L, et al. Prevalence of gluten-related disorders in Asia-Pacific region: a systematic review. J Gastrointestin Liver Dis 2019;28:95-105.

Ahadi Z, Shafiee G, Razmandeh R, Keshtkar A-A, Sani MN, Azemati B, et al. Prevalence of celiac disease among the Iranian population: A systematic review and meta-analysis of observational studies. Turk J Gastroenterol 2016;27:122-8.

Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.

Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S, et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 2003;362:30-7.

Faghih M, Rostami-Nejad M, Amani D, Sadeghi A, Pourhoseingholi MA, Masotti A, et al. Analysis of IL17A and IL21 Expression in the Small Intestine of Celiac Disease Patients and Correlation with Circulating Thioredoxin Level. Genet Test Mol Biomarkers 2018;22:518-25.

du Pre MF, Sollid LM. T-cell and B-cell immunity in celiac disease. Best Pract Res Clin Gastroenterol 2015;29:413-23.

Bjorck S, Lindehammer SR, Fex M, Agardh D. Serum cytokine pattern in young children with screening detected coeliac disease. Clin Exp Immunol 2015;179:230-5.

Ma X, Yan W, Zheng H, Du Q, Zhang L, Ban Y, et al. Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells. F1000Res 2015;4.

Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev 2008;226:205-18.

Liu J, Cao S, Kim S, Chung EY, Homma Y, Guan X, et al. Interleukin-12: an update on its immunological activities, signaling and regulation of gene expression. Curr Immunol Rev 2005;1:119-37.

Viallard JF, Pellegrin JL, Ranchin V, Schaeverbeke T, Dehais J, Longy-Boursier M, et al. Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1999;115:189-95.

Weiss JM, Subleski JJ, Wigginton JM, Wiltrout RH. Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin Biol Ther 2007;7:1705-21.

Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 2012;32:23-63.

Wong R, Wilson R, Steele R, Radford-Smith G, Adelstein S. A comparison of 13 guinea pig and human anti-tissue transglutaminase antibody ELISA kits. Journal of clinical pathology 2002;55:488-94.

Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, et al. Structural basis for gluten intolerance in celiac sprue. Science 2002;297:2275-9.

Abadie V, Sollid LM, Barreiro LB, Jabri B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu Rev Immunol 2011;29:493-525.

Claeskens G, Aerts M, Molenberghs G. A quadratic bootstrap method and improved estimation in logistic regression. Statistics & probability letters 2003;61:383-94.

Potter DM. A permutation test for inference in logistic regression with small‐and moderate‐sized data sets. Statistics in medicine 2005;24:693-708.

Pearce J, Ferrier S. An evaluation of alternative algorithms for fitting species distribution models using logistic regression. Ecological modelling 2000;128:127-47.

Maiti T, Pradhan V. Bias reduction and a solution for separation of logistic regression with missing covariates. Biometrics 2009;65:1262-9.

Schulz EM, Betebenner D, Ahn M. Hierarchical logistic regression in course placement. Journal of Educational Measurement 2004;41:271-86.

Gordóvil Merino A, Guàrdia Olmos J, Peró M. Estimation of logistic regression models in small samples. A simulation study using a weakly informative default prior distribution. Psicologica, 2012, vol 33, num 2, p 345-361 2012.

Heydari F, Rostami-Nejad M, Moheb-Alian A, Mollahoseini MH, Rostami K, Pourhoseingholi MA, et al. Serum cytokines profile in treated celiac disease compared with non-celiac gluten sensitivity and control: a marker for differentiation. Journal of Gastrointestinal & Liver Diseases 2018;27.

Glickman ME, Van Dyk DA. Basic bayesian methods. Topics in Biostatistics: Springer; 2007. p. 319-38.

Gamerman D, Lopes HF. Markov chain Monte Carlo: stochastic simulation for Bayesian inference: Chapman and Hall/CRC; 2006.

Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011;117:3720-32.

Fornari MC, Pedreira S, Niveloni S, Gonzalez D, Diez RA, Vazquez H, et al. Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia? Am J Gastroenterol 1998;93:413-8.

Seppola M, Larsen AN, Steiro K, Robertsen B, Jensen I. Characterisation and expression analysis of the interleukin genes, IL-1β, IL-8 and IL-10, in Atlantic cod (Gadus morhua L.). Molecular immunology 2008;45:887-97.

Ferguson-Smith AC, Chen YF, Newman MS, May LT, Sehgal PB, Ruddle FH. Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21. Genomics 1988;2:203-8.

Di Sabatino A, Giuffrida P, Fornasa G, Salvatore C, Vanoli A, Naviglio S, et al. Innate and adaptive immunity in self-reported nonceliac gluten sensitivity versus celiac disease. Dig Liver Dis 2016;48:745-52.

Goel G, Tye-Din JA, Qiao SW, Russell AK, Mayassi T, Ciszewski C, et al. Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv 2019;5:eaaw7756.

Vorobjova T, Tagoma A, Oras A, Alnek K, Kisand K, Talja I, et al. 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. J Immunol Res 2019;2019:6179243.

Bjorck S, Brundin C, Karlsson M, Agardh D. Reduced Bone Mineral Density in Children With Screening-detected Celiac Disease. J Pediatr Gastroenterol Nutr 2017;65:526-32.

Kordulewska NK, Kostyra E, Piskorz-Ogorek K, Moszynska M, Cieslinska A, Fiedorowicz E, et al. Serum cytokine levels in children with spectrum autism disorder: Differences in pro- and anti-inflammatory balance. J Neuroimmunol 2019;337:577066.

Schoenborn JR, Wilson CB. Regulation of interferon‐γ during innate and adaptive immune responses. Advances in immunology 2007;96:41-101.

Lopez-Palacios N, Pascual V, Castano M, Bodas A, Fernandez-Prieto M, Espino-Paisan L, et al. Evaluation of T cells in blood after a short gluten challenge for coeliac disease diagnosis. Dig Liver Dis 2018;50:1183-8.

Marafini I, Monteleone I, Di Fusco D, Cupi ML, Paoluzi OA, Colantoni A, et al. TNF-alpha Producing Innate Lymphoid Cells (ILCs) Are Increased in Active Celiac Disease and Contribute to Promote Intestinal Atrophy in Mice. PLoS One 2015;10:e0126291.

DOI: https://doi.org/10.22037/ghfbb.v12i0.1826