Serum levels of the interferon-γ-inducing cytokine interleukin-18 are increased in individuals at high risk of developing Type I diabetes

被引:91
作者
Nicoletti, F
Conget, I
Di Marco, R
Speciale, AM
Morìngo, R
Bendtzen, K
Gomis, R
机构
[1] Univ Milan, Dept Clin Med Prevent & Biotechnol Hlth, Milan, Italy
[2] Univ Barcelona, Hosp Clin Barcelona, Fac Med,Endocrinol & Diabet Unit, IDIBAPS,Inst Biomed Studies August Pri I Sunyer, Barcelona, Spain
[3] Univ Catania, Dept Microbiol & Gynecol Sci, Catania, Italy
[4] Rigshosp Univ Hosp, Inst Inflammat Res, Copenhagen, Denmark
关键词
interleukin-18; serum levels; interferon-gamma;
D O I
10.1007/s001250051619
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Interleukin (IL)-18 is a cytokine primarily produced by macrophages and capable of inducing T lymphocyte synthesis of interferon (IFN)-gamma. An up-regulated synthesis of IFN-gamma with consequential Type I cytokine dominance has been repeatedly shown in Type I (insulin-dependent) diabetes mellitus and thought to be involved in its pathogenesis. Because increased production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18, we compared the circulating levels of IL-18 in patients with newly diagnosed Type I diabetes with those of non-diabetic first-degree relatives and healthy control subjects. Methods. Serum samples were obtained from healthy control subjects, patients with newly diagnosed Type I diabetes, and their healthy first-degree relatives. The latter were subdivided into "low" and "high" risk prediabetics depending on whether they were negative or positive for two or more of the anti-pancreatic autoantibodies ICA, GAD, IA-2 and IAA. Serum levels of IL-18 were measured by solid-phase ELISA. Results. Interleukin (IL)-18 was above the detection limit of 25 pg/ml in 7 of 40 (17 %) healthy control subjects, in 5 of 35 (14 %) patients and in 3 of 30 (10 %) first-degree relatives at low risk of developing Type I diabetes. In contrast, IL-18 could be detected in 19 of 28 (68 %; p < 0.0001) relatives at high risk. The mean serum level of IL-18 was higher in these individuals when compared with the low-risk relatives, patients and control subjects. Conclusion/interpretation. IL-18 serum levels are increased selectively during the early, subclinical stage of Type I diabetes.
引用
收藏
页码:309 / 311
页数:3
相关论文
共 10 条
  • [1] IL-18:: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family
    Dinarello, CA
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1999, 103 (01) : 11 - 24
  • [2] Hussain MJ, 1996, DIABETOLOGIA, V39, P60
  • [3] Cytokine secretion patterns in twins discordant for Type I diabetes
    Kallmann, BA
    Lampeter, EF
    Hanifi-Moghaddam, P
    Hawa, M
    Leslie, RDG
    Kolb, H
    [J]. DIABETOLOGIA, 1999, 42 (09) : 1080 - 1085
  • [4] Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients
    Karlsson, MGE
    Lawesson, SS
    Ludvigsson, J
    [J]. DIABETOLOGIA, 2000, 43 (06) : 742 - 749
  • [5] DETECTION OF AUTOANTIBODIES TO THE 65-KD ISOFORM OF GLUTAMATE-DECARBOXYLASE BY RADIOIMMUNOASSAY
    LUHDER, F
    WOLTANSKI, KP
    MAUCH, L
    HAUBRUCK, H
    KOHNERT, KD
    RJASANOWSKI, I
    MICHAELIS, D
    ZIEGLER, M
    [J]. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 1994, 130 (06) : 575 - 580
  • [6] Autoantibodies to IA-2 in insulin-dependent diabetes mellitus - Measurements with a new immunoprecipitation assay
    Masuda, M
    Powell, M
    Chen, S
    Beer, C
    Fichna, P
    Smith, BR
    Furmaniak, J
    [J]. CLINICA CHIMICA ACTA, 2000, 291 (01) : 53 - 66
  • [7] Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis
    Nicoletti, F
    Patti, F
    Cocuzza, C
    Zaccone, P
    Nicoletti, A
    DiMarco, R
    Reggio, A
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1996, 70 (01) : 87 - 90
  • [8] Heterophile anti-mouse immunoglobulin antibodies may interfere with cytokine measurements in patients with HLA alleles protective for type 1A diabetes
    Redondo, MJ
    Gottlieb, PA
    Motheral, T
    Mulgrew, C
    Rewers, M
    Babu, S
    Stephens, E
    Wegmann, DR
    Eisenbarth, GS
    [J]. DIABETES, 1999, 48 (11) : 2166 - 2170
  • [9] Rothe H, 1999, J IMMUNOL, V163, P1230
  • [10] COMPETITIVE INSULIN AUTOANTIBODY ASSAY - PROSPECTIVE EVALUATION OF SUBJECTS AT HIGH-RISK FOR DEVELOPMENT OF TYPE-1 DIABETES-MELLITUS
    VARDI, P
    DIB, SA
    TUTTLEMAN, M
    CONNELLY, JE
    GRINBERGS, M
    RADIZABEH, A
    RILEY, WJ
    MACLAREN, NK
    EISENBARTH, GS
    SOELDNER, JS
    [J]. DIABETES, 1987, 36 (11) : 1286 - 1291