본문 바로가기
KERD
논문KCI 등재

제 1형 당뇨병으로 진단된 소아 및 청소년 환자의 사이토카인 농도 분석

Analysis of Cytokines in Sera from Type 1 Diabetic Patients at Diagnosis

신충호|양세원|유인석
대한소아내분비학회 (Korean Society Of Pediatric Endocrinology)|2011.04|Annals of Pediatric Endocrinology & Metabolism|제16권 제1호|pp. 13-19

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

Diabetes mellitus
주제분류소아과학

초록

목 적:1형 당뇨병은 T세포 매개의 면역질환으로서 다양한 사이토카인이 여러 기전으로 병리기전에 관여하고 있다. 저자는 지금까지 1형 당뇨병에 발병 및 진행에 관여하는 것으로 알려진 여러 가지 사이토카인을 분석을 통해 인체 내에서 1형 당뇨병의 병리기전을 알아보고자 하였다. 방 법:2004년 1월부터 2009년 7월까지 서울대학교병원 소아청소년과에서 새롭게 진단된 25명의 환자와 동 기간 타 병원에서 진단 후 1개월 이내에 전원 된 13명의 환자의 혈청을 진단 시 또는 진단 후 1개월 이내에 채혈된 혈액에서 분석하여 39명의 건강한 대조군과 비교하였다. 결 과:새롭게 진단된 제 1형 당뇨병 환자는 대조군과 비교하여 혈청에서의 친염증성 사이토카인인 IL-1β (P˂0.01), TNF-α (P=0.019)의 농도가 유의하게 높았으며 IL-10 (P˂0.01) 농도 또한 유의하게 높았다. 인슐린 자가항체 양성인 환자는 21명(60%)이며 인슐린 자가항체의 농도는 IL-10 (r= 0.454, P=0.006), TNF- α (r=0.368, P=0.030)와 유의한 양의 상관관계를 보였다. 결 론:제 1형 당뇨병의 발병 시 친염증성 사이토카인인 IL-1β, TNF-α과 2형 사이토카인 IL-10이 병리기전에 중요한 역할을 하는 것으로 생각된다.

Abstract

Purpose:Diverse cytokines influence the pathogenesis of type 1 diabetes mellitus (T1DM) in different ways. We studied the profile of cytokines in sera from type 1 diabetic patients at diagnosis. Methods:Serum levels of 11 cytokines (IL-1α, IL-1β, IL-1Ra, IL-2, IL-4, IL-6, IL-10, IL-12(p70), INF-γ, and TNF-α) from 38 newly-diagnosed T1DM patents and 39 healthy controls were measured, using multiplex immunoanalytic xMAP. Results:Patients showed significantly higher levels of IL-1β (P˂0.01), IL-10 (P˂0.01), and TNF-α (P=0.019), than the healthy controls. In 12 of 35 patients, the insulin autoantibody (IAA) was positive (34%) and the level of IAA was correlated with IL-10 (r=0.454, P=0.006), and TNF-α (r=0.368, P=0.030). Conclusion:These results suggest that IL-1β, TNF-α, and IL-10 play a role in the pathogenesis of T1DM, and the level of the IAA is correlated with IL-10 and TNF-α. (J Korean Soc Pediatr Endocrinol 2011;16:13-19)

참고문헌 (41)

  1. Klöppel G, "Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited", Surv Synth Pathol Res, 4, pp.110~125 (1985)
  2. Eizirik DL, "A choice of death-the signal- transduction of immune-mediated beta-cell apoptosis", Diabetologia, 44, pp.2115~2133 (2001)
  3. Rabinovitch A, "An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus", Diabetes Metab Rev, 14, pp.129~151 (1998)
  4. Jörns A, "Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1", Ztm-iddm rat, 2005, pp.54, 2041~2052
  5. Cavallo MG, "Cytokines in sera from insulin-dependent diabetic patients at diagnosis", Clin Exp Immunol, 86, pp.256~259 (1991)
  6. Hussain MJ, "Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM", Diabetologia, 39, pp.60~69 (1996)
  7. Kallmann BA, "Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease", Diabetes, 46, pp.237~243 (1997)
  8. Mandrup-Poulsen T, "The role of interleukin-1 in the pathogenesis of IDDM", Diabetologia, 39, pp.1005~1029 (1996)
  9. Hansen BS, "Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets", Biomed Biochim Acta, 47, pp.305~309 (1988)
  10. Maedler K, "Low concentration of interleukin- 1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets", Diabetes, 55, pp.2713~2722 (2006)
  11. Berchtold LA, "IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes", Eur Cytokine Netw, 20, pp.81~87 (2009)
  12. Larsen CM, "Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes", Diabetes Care, 32, pp.1663~1668 (2009)
  13. Schloot NC, "Association of immune mediators at diagnosis of Type 1 diabetes with later clinical remission", Diabet Med, 24, pp.512~520 (2007)
  14. Holden RJ, "Tumor necrosis factor- alpha: a continuum of liability between insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus and carcinoma", Med Hypotheses, 52, pp.319~323 (1999)
  15. Christen U, "A dual role for TNF-alpha in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis", J Immunol, 166, pp.7023~7032 (2001)
  16. Rabinovitch A, "Roles of cytokines in the pathogenesis and therapy of type 1 diabetes", Cell Biochem Biophys, 48, pp.159~163 (2007)
  17. Gaffen SL, "Overview of interleukin-2 function, production and clinical applications", Cytokine, 28, pp.109~123 (2004)
  18. Vella A, "Localization of a type 1 diabetes locus in the IL2RA", CD25 region by use of tag single-nucleotide polymorphisms, 2005, pp.76, 773~779
  19. Rabinovitch A, "Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice", Diabetes, 51, pp.638~645 (2002)
  20. Ozer G, "Serum IL-1, IL-2, TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings", J Pediatr Endocrinol Metab, 16, pp.203~210 (2003)
  21. Trembleau S, "IL-12 administration accelerates autoimmune diabetes in both wild-type and IFN-gamma-deficient nonobese diabetic mice, revealing pathogenic and protective effects of IL-12-induced IFN-gamma", J Immunol, 170, pp.5491~5501 (2003)
  22. Donath MY, "Cytokines and beta-cell biology: from concept to clinical translation", Endocr Rev, 29, pp.334~350 (2008)
  23. Kamimura D, "IL-6 signal transduction and its physiological roles: the signal orchestration model", Rev Physiol Biochem Pharmacol, 149, pp.1~38 (2003)
  24. Wadt KA, "Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase", Diabetes, 47, pp.1602~1608 (1998)
  25. Sandler S, "Interleukin-6 affects insulin secretion and glucose metabolism of rat pancreatic islets in vitro", Endocrinology, 126, pp.1288~1294 (1990)
  26. Rabinovitch A, "Role of cytokines in the pathogenesis of autoimmune diabetes mellitus", Rev Endocr Metab Disord, 4, pp.291~299 (2003)
  27. Spolski R, "Interleukin-21: basic biology and implications for cancer and autoimmunity", Annu Rev Immunol, 26, pp.57~79 (2008)
  28. Monteleone G, "Interleukin-21 (IL- 21)-mediated pathways in T cell-mediated disease", Cytokine Growth Factor Rev, 20, pp.185~191 (2009)
  29. Sutherland AP, "Interleukin-21 is required for the development of type 1 diabetes in NOD mice", Diabetes, 58, pp.1144~1155 (2009)
  30. Spolski R, "IL-21 signaling is critical for the development of type I diabetes in the NOD mouse", Proc Natl Acad Sci USA, 105, pp.14028~14033 (2008)
  31. Romagnani S, "The Th1", Th2 paradigm, 1997, pp.18, 263~266
  32. Mason D, "T-cell subsets in autoimmunity", Current Opin Immunol, 5, pp.728~732 (1992)
  33. Berman MA, "Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus", J Immunol, 157, pp.4690~4696 (1996)
  34. Pennline KJ, "Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse", Clin Immunol Immunopathol, 71, pp.169~175 (1994)
  35. Wogensen L, "Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice", J Exp Med, 179, pp.1379~1384 (1994)
  36. Pakala SV, "T helper 2 (Th2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice", J Exp Med, 186, pp.299~306 (1997)
  37. Balasa B, "A mechanism for IL-10-mediated diabetes in the nonobese diabetic (NOD) mouse: ICAM-1 deficiency blocks accelerated diabetes", J Immunol, 165, pp.7330~7337 (2000)
  38. Gregg RK, "IL-10 diminishes CTLA-4 expression on islet-resident T cells and sustains their activation rather than tolerance", J Immunol, 174, pp.662~670 (2005)
  39. Gately MK, "The interleukin-12", interleukin-12-receptor system: role in normal and pathologic immune responses, 1998, pp.16, 495~521
  40. Trembleau S, "Pancreas-infiltrating Th1 cells and diabetes develop in IL-12-deficient nonobese diabetic mice", J Immunol, 163, pp.2960~2968 (1999)
  41. Taplin CE, "Autoantibodies in type 1 diabetes", Autoimmunity, 41, pp.11~18 (2008)

관련 논문AI추천

소아의 1형 및 2형 당뇨병 감별에 있어서 임상적 특징 및 자가 항체 검사의 유용성박지윤, 오종석, 유지숙대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2011 · 제16권 제2호Impacts of circulating cytokine levels and gene polymorphism predisposition on type 1 diabetes mellitusAlghamdi Ahmed H., El-Refaei Mohamed F., El-Sherbini Sherif M., Mady Essam A., Shatla Ibrahim M.대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2024 · 제29권 제4호소아청소년 연령에서 발생한 2형 당뇨병의 항췌도 자가항체 유무에 따른 임상적 특성김덕희, 김호성, 지민철, 채현욱대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2010 · 제15권 제2호2001-2008년 진단된 소아당뇨병의 분포와 특징고철우, 박준석, 이환석, 조민현, 홍은희대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2009 · 제14권 제2호Fasting serum C-peptide is useful for initial classification of diabetes mellitus in children and adolescents김민선, 김은영, 김종덕, 김찬종, 이대열, 조민정대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2014 · 제19권 제2호Preserved C-peptide levels in overweight or obese compared with underweight children upon diagnosis of type 1 diabetes mellitus신충호, 양세원, 이영아, 이윤정, 조원임, Hyeoh Won Yu대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2015 · 제20권 제2호

이 간행물의 다른 논문 (10건)

소아기에 발병한 성장호르몬결핍증 환자의 성인기에서의 재평가 및 성장호르몬 치료: 청소년기에서 성인기로의 이행기의 관리유한욱, 최진호pp. 1-6약물 전달 시스템-소아내분비 영역과 관련하여이지은pp. 7-12성선자극호르몬방출호르몬 유도체 치료를 받는 진성성조숙증 여아의 1년간 IGF-1, IGFBP-3 혈중농도의 변화이경희pp. 20-23Insulin-Like Growth Factor Binding Protein-3가 3T3-L1 지방세포의 adipokine과 유전자 발현에 미치는 영향김혜순pp. 24-30불현성 갑상샘 저하증 소아청소년의 IGF-I과 IGFBP-3를 이용한 성장 상태 평가배재욱, 곽병옥, 정소정pp. 31-37
원문 보기