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PMID: 10377182 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis.

The Journal of experimental medicine ·Vol. 189 ·No. 12 ·1999-06-21 ·Pages 1863-74

Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, Davidson RN, Toossi Z

Abstract

Several lines of evidence suggest that host genetic factors controlling the immune response influence infection by Mycobacterium tuberculosis. The proinflammatory cytokine interleukin (IL)-1beta and its antagonist, IL-1Ra (IL-1 receptor agonist), are strongly induced by M. tuberculosis and are encoded by polymorphic genes. The induction of both IL-1Ra mRNA and secreted protein by M. tuberculosis in IL-1Ra allele A2-positive (IL-1Ra A2(+)) healthy subjects was 1.9-fold higher than in IL-1Ra A2(-) subjects. The M. tuberculosis-induced expression of mRNA for IL-1beta was higher in subjects of the IL-1beta (+3953) A1(+) haplotype (P = 0.04). The molar ratio of IL-1Ra/IL-1beta induced by M. tuberculosis was markedly higher in IL-1Ra A2(+) individuals (P < 0.05), with minor overlap between the groups, reflecting linkage between the IL-1Ra A2 and IL-1beta (+3953) A2 alleles. In M. tuberculosis-stimulated peripheral blood mononuclear cells, the addition of IL-4 increased IL-1Ra secretion, whereas interferon gamma increased and IL-10 decreased IL-1beta production, indicative of a differential influence on the IL-1Ra/IL-1beta ratio by cytokines. In a study of 114 healthy purified protein derivative-reactive subjects and 89 patients with tuberculosis, the frequency of allelic variants at two positions (-511 and +3953) in the IL-1beta and IL-1Ra genes did not differ between the groups. However, the proinflammatory IL-1Ra A2(-)/IL-1beta (+3953) A1(+) haplotype was unevenly distributed, being more common in patients with tuberculous pleurisy (92%) in comparison with healthy M. tuberculosis-sensitized control subjects or patients with other disease forms (57%, P = 0.028 and 56%, P = 0. 024, respectively). Furthermore, the IL-1Ra A2(+) haplotype was associated with a reduced Mantoux response to purified protein derivative of M. tuberculosis: 60% of tuberculin-nonreactive patients were of this type. Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of delayed-type hypersensitivity and disease expression in human tuberculosis.

MeSH Terms
Cell Division/genetics,immunology Genotype Haplotypes/genetics Humans Hypersensitivity, Delayed/genetics,immunology Interleukin 1 Receptor Antagonist Protein Interleukin-1/antagonists & inhibitors,genetics Interleukin-10/pharmacology Interleukin-4/pharmacology Interleukin-6/pharmacology Leukocytes/immunology,metabolism Mycobacterium tuberculosis/genetics,immunology Polymorphism, Genetic RNA, Messenger/genetics Receptors, Interleukin-1/antagonists & inhibitors Sialoglycoproteins/genetics Tuberculin/immunology Tuberculosis/genetics,immunology
Chemicals
IL1RN protein, human Interleukin 1 Receptor Antagonist Protein Interleukin-1 Interleukin-6 RNA, Messenger Receptors, Interleukin-1 Sialoglycoproteins Tuberculin Interleukin-10 Interleukin-4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wilkinson R J
Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio 44106-4984, USA.
Patel P
Llewelyn M
Hirsch C S
Pasvol G
Snounou G
Davidson R N
Toossi Z
References (53)
53 references, click to expand
  1. Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components.
    J Clin Invest. 1995 Feb;95(2):586-92 PMID: 7860742
  2. Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis.
    J Immunol. 1990 Jul 1;145(1):149-54 PMID: 2113553
  3. Cerebrospinal fluid interleukin-1 beta/interleukin-1 receptor antagonist balance and tumor necrosis factor-alpha concentrations in tuberculous, viral and acute bacterial meningitis.
    Scand J Infect Dis. 1994;26(6):667-74 PMID: 7747089
  4. Decreased production of TGF-beta 1 by human alveolar macrophages compared with blood monocytes.
    J Immunol. 1996 May 1;156(9):3461-8 PMID: 8617974
  5. Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production.
    Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3193-8 PMID: 8622912
  6. Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11008-13 PMID: 8855299
  7. AF12198, a novel low molecular weight antagonist, selectively binds the human type I interleukin (IL)-1 receptor and blocks in vivo responses to IL-1.
    J Biol Chem. 1996 Nov 29;271(48):30517-23 PMID: 8940020
  8. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection.
    N Engl J Med. 1996 Dec 26;335(26):1941-9 PMID: 8960473
  9. Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guérin infection.
    N Engl J Med. 1996 Dec 26;335(26):1956-61 PMID: 8960475
  10. Increased inflammatory cytokines and new collagen formation in cutaneous tuberculosis and sarcoidosis.
    Thorax. 1996 Dec;51(12):1253-61 PMID: 8994525
  11. Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes.
    Eur J Immunol. 1997 Jan;27(1):171-7 PMID: 9022014
  12. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3926-31 PMID: 9108081
  13. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9869-74 PMID: 9275218
  14. Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response.
    J Immunol. 1997 Sep 15;159(6):3034-43 PMID: 9300729
  15. An epidemic of tuberculosis with a high rate of tuberculin anergy among a population previously unexposed to tuberculosis, the Yanomami Indians of the Brazilian Amazon.
    Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13227-32 PMID: 9371828
  16. An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis.
    N Engl J Med. 1998 Mar 5;338(10):633-9 PMID: 9486991
  17. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans.
    N Engl J Med. 1998 Mar 5;338(10):640-4 PMID: 9486992
  18. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro.
    Scand J Immunol. 1998 Mar;47(3):195-8 PMID: 9519856
  19. Adequate expression of protective immunity in the absence of granuloma formation in Mycobacterium tuberculosis-infected mice with a disruption in the intracellular adhesion molecule 1 gene.
    Infect Immun. 1998 Apr;66(4):1666-70 PMID: 9529096
  20. Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions.
    J Leukoc Biol. 1998 Apr;63(4):440-50 PMID: 9544573
  21. Tumor necrosis factor and interleukin-1 inhibitors as markers of disease activity of tuberculosis.
    Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1328-31 PMID: 9563758
  22. Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion.
    J Exp Med. 1998 May 4;187(9):1463-75 PMID: 9565638
  23. Interleukin-1 receptor antagonist: role in biology.
    Annu Rev Immunol. 1998;16:27-55 PMID: 9597123
  24. The immunogenetics of human infectious diseases.
    Annu Rev Immunol. 1998;16:593-617 PMID: 9597143
  25. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency.
    Science. 1998 May 29;280(5368):1432-5 PMID: 9603732
  26. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.
    Science. 1998 May 29;280(5368):1435-8 PMID: 9603733
  27. Mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection.
    J Clin Invest. 1998 Jun 1;101(11):2364-9 PMID: 9616207
  28. Geographical distribution of tuberculosis notifications in national surveys of England and Wales in 1988 and 1993: report of the Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group.
    Thorax. 1998 Mar;53(3):176-81 PMID: 9659351
  29. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes.
    Eur J Immunol. 1998 Aug;28(8):2598-602 PMID: 9710237
  30. Peptide-specific T cell response to Mycobacterium tuberculosis: clinical spectrum, compartmentalization, and effect of chemotherapy.
    J Infect Dis. 1998 Sep;178(3):760-8 PMID: 9728545
  31. Differential regulation of Th1 and Th2 cells by p91-110 and p21-40 peptides of the 16-kD alpha-crystallin antigen of Mycobacterium tuberculosis.
    Clin Exp Immunol. 1998 Dec;114(3):392-7 PMID: 9844048
  32. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection.
    J Clin Invest. 1998 Dec 15;102(12):2035-40 PMID: 9854038
  33. Genetic epidemiology of infectious diseases in humans: design of population-based studies.
    Emerg Infect Dis. 1998 Oct-Dec;4(4):593-603 PMID: 9866735
  34. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene.
    J Infect Dis. 1999 Mar;179(3):721-4 PMID: 9952386
  35. Genetics and resistance to tuberculosis. Could resistance be enhanced by genetic engineering?
    Ann Intern Med. 1992 Jun 1;116(11):937-41 PMID: 1580452
  36. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro.
    Eur J Clin Invest. 1992 Jun;22(6):396-402 PMID: 1353022
  37. Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta).
    Hum Mol Genet. 1992 Sep;1(6):450 PMID: 1301918
  38. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat.
    Hum Genet. 1993 May;91(4):403-4 PMID: 8500797
  39. Cytokine production at the site of disease in human tuberculosis.
    Infect Immun. 1993 Aug;61(8):3482-9 PMID: 8335379
  40. Interleukin-1 receptor antagonist.
    Adv Immunol. 1993;54:167-227 PMID: 8379462
  41. Interleukin-1 is involved in mouse resistance to Mycobacterium avium.
    Infect Immun. 1994 Feb;62(2):457-61 PMID: 8300206
  42. Evaluation of tuberculin reactivity in BCG-immunized siblings.
    Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):620-4 PMID: 8118628
  43. Interleukin 1 receptor antagonist production in human monocytes is induced by IL-1 alpha, IL-3, IL-4 and GM-CSF.
    Cytokine. 1993 Sep;5(5):407-15 PMID: 8142595
  44. Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens.
    Immunology. 1994 Feb;81(2):171-6 PMID: 8157267
  45. Tuberculin reactivity after newborn BCG immunization in mono- and dizygotic twins.
    Tuber Lung Dis. 1994 Apr;75(2):138-43 PMID: 8032047
  46. Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1.
    J Infect Dis. 1994 Nov;170(5):1229-37 PMID: 7963718
  47. Induction by transforming growth factor-beta 1 of the interleukin-1 receptor antagonist and of its intracellular form in human polymorphonuclear cells.
    Eur J Immunol. 1994 Dec;24(12):3194-8 PMID: 7805748
  48. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism.
    Clin Exp Immunol. 1995 Feb;99(2):303-10 PMID: 7851026
  49. Assessment of the interleukin 1 gene cluster and other candidate gene polymorphisms in host susceptibility to tuberculosis.
    Tuber Lung Dis. 1998;79(2):83-9 PMID: 10645445
  50. Tuberculosis in twins: a re-analysis of the Prophit survey.
    Am Rev Respir Dis. 1978 Apr;117(4):621-4 PMID: 565607
  51. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis.
    J Immunol. 1989 Feb 15;142(4):1114-9 PMID: 2464638
  52. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection.
    Cell. 1989 Mar 10;56(5):731-40 PMID: 2647299
  53. BCG-induced granuloma formation in murine tissues.
    Immunobiology. 1994 Oct;191(4-5):369-77 PMID: 7713550
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.189.12.1863
Published
1999-06-21
Pages
1863-74
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192963
Subset
IM
Grants
NIAID NIH HHS · AI-18471 · United States
External Links
PubMed source DOI: 10.1084/jem.189.12.1863 PMC Full Text View journal details
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