Advertisement

Impact of Genomic Variations on Inflammatory Processes and Sepsis

  • Frank Stüber
Part of the Perspectives on Critical Care Infectious Diseases book series (CCID, volume 2)

Abstract

The immune response to injury involves a complex pattern of primary, secondary and tertiary humoral and cellular responses. Genetic variability in the expression of the mediators comprising these responses constitutes the genetic background which may potentially influence the course of inflammation in each individual. Differences in this background may in part explain the highly variable clinical courses noted among septic patients. Comparable doses of infecting microbes may induce a wide range of severity of illness due in part to genetic variability.

Keywords

Septic Shock Severe Sepsis Cerebral Malaria Single Base Change Tumor Necrosis Factor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sasse KC, Nauenberg E, Long A, Anton B, Tucker HJ, Hu TW. Long-term survival after intensive care unit admission with sepsis. Crit Care Med 1995;23:1040–1047.PubMedCrossRefGoogle Scholar
  2. 2.
    Edmiston CE, Jr., Condon RE. Bacterial translocation. Surg Gynecol Obstet 1991;173:73–83.PubMedGoogle Scholar
  3. 3.
    Blackwell TS, Christman JW. Sepsis and cytokines. current status. Br J Anaesth 1996;77:110–117.PubMedCrossRefGoogle Scholar
  4. 4.
    Bernard GR, Wheeler AP, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson WJ, Wright PE, Christman BW, Dupont WD, Higgins SB, Swindell BB. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 1997;336:912–918.PubMedCrossRefGoogle Scholar
  5. 5.
    van der Poll T, de Waal Malefyt R, Coyle SM, Lowry SF. Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: sequential measurements of plasma soluble interleukin (IL)-l receptor type II, IL-10, and IL-13. J Infect Dis 1997;175:118–122.PubMedCrossRefGoogle Scholar
  6. 6.
    Volk HD, Reinke P, Krausch D, Zuckermann H, Asadullah K, Muller JM, Docke WD, Kox WJ. Monocyte de activation—rationale for a new therapeutic strategy in sepsis. Intensive Care Med 1996;22 Suppl 4:S474–481.PubMedCrossRefGoogle Scholar
  7. 7.
    Fisher CJ, Jr., Slotman GJ, Opal SM, Pribble JP, Bone RC, Emmanuel G, Ng D, Bloedow DC, Catalano MA. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. The IL-IRA Sepsis Syndrome Study Group. Crit Care Med 1994;22:12–21.PubMedGoogle Scholar
  8. 8.
    Docke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 1997;3:678–681.PubMedCrossRefGoogle Scholar
  9. 9.
    Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP, et al. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature 1984;312:721–724.PubMedCrossRefGoogle Scholar
  10. 10.
    Weinberg JR, Boyle P, Meager A, Guz A. Lipopolysaccharide, tumor necrosis factor, and interleukin-1 interact to cause hypotension. J Lab Clin Med 1992; 120:205–211.PubMedGoogle Scholar
  11. 11.
    Westendorp RG, Langermans JA, Huizinga TW, Elouali AH, Verweij CL, Boomsma DI, Vandenbrouke JP. Genetic influence on cytokine production and fatal meningococcal disease. Lancet 1997;349:170–173.PubMedCrossRefGoogle Scholar
  12. 12.
    Whichelow CE, Hitman GA, Raafat I, Bottazzo GF, Sachs JA. The effect of TNF*B gene polymorphism on TNF-alpha and-beta secretion levels in patients with insulin-dependent diabetes mellitus and healthy controls. Eur J Immunogenet 1996;23:425–435.PubMedCrossRefGoogle Scholar
  13. 13.
    Kato T, Honda M, Kuwata S, Juji T, Kunugi H, Nanko S, Fukuda M, Honda Y. Novel polymorphism in the promoter region of the tumor necrosis factor alpha gene: No association with narcolepsy. Am J Med Genet 1999;88:301–304.PubMedCrossRefGoogle Scholar
  14. 14.
    Knight JC, Udalova I, Hill AV, Greenwood BM, Peshu N, Marsh K, Kwiatkowski D. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 1999;22:145–150.PubMedCrossRefGoogle Scholar
  15. 15.
    Wilson AG, di Giovine FS, Blakemore AI, Duff GW. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by Ncol restriction of PCR product. Hum Mol Genet 1992;l:353–353.CrossRefGoogle Scholar
  16. 16.
    Brinkman BM, Huizinga TW, Kurban SS, van der Velde EA, Schreuder GM, Hazes JM, Breedveld FC, Verweij CL. Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease? Br J Rheumatol 1997;36:516–521.PubMedCrossRefGoogle Scholar
  17. 17.
    McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 1994;371:508–510.PubMedCrossRefGoogle Scholar
  18. 18.
    Stirnadel HA, Stockle M, Feiger I, Smith T, Tanner M, Beck HP. Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania. Trop Med Int Health 1999;4:187–193.PubMedCrossRefGoogle Scholar
  19. 19.
    Pociot F, Wilson AG, Nerup J, Duff GW. No independent association between a tumor necrosis factor-alpha promotor region polymorphism and insulin-dependent diabetes mellitus. Eur J Immunol 1993;23:3050–3053.PubMedCrossRefGoogle Scholar
  20. 20.
    Wilson AG, Gordon C, di Giovine FS, de Vries N, van de Putte LB, Emery P, Duff GW. A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha. Eur J Immunol 1994;24:191–195.PubMedCrossRefGoogle Scholar
  21. 21.
    Stuber F, Udalova IA, Book M, Drutskaya LN, Kuprash DV, Turetskaya RL, Schade FU, Nedospasov SA.-308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter. J Inflamm 1995;46:42–50.PubMedGoogle Scholar
  22. 22.
    Brinkman BM, Zuijdeest D, Kaijzel EL, Breedveld FC, Verweij CL. Relevance of the tumor necrosis factor alpha (TNF alpha)-308 promoter polymorphism in TNF alpha gene regulation. J Inflamm 1995;46:32–41.PubMedGoogle Scholar
  23. 23.
    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 1997;94:3195–3199.PubMedCrossRefGoogle Scholar
  24. 24.
    Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, Cheval C, Monchi M, Teboul JL, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA 1999;282:561–568.PubMedCrossRefGoogle Scholar
  25. 25.
    Pociot F, Molvig J, Wogensen L, Worsaae H, Dalboge H, Baek L, Nerup J. A tumour necrosis factor beta gene polymorphism in relation to monokine secretion and insulin-dependent diabetes mellitus. Scand J Immunol 1991;33:37–49.PubMedCrossRefGoogle Scholar
  26. 26.
    Bettinotti MP, Hartung K, Deicher H, Messer G, Keller E, Weiss EH, Albert ED. Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes. Immunogenetics 1993;37:449–454.PubMedCrossRefGoogle Scholar
  27. 27.
    Badenhoop K, Schwarz G, Trowsdale J, Lewis V, Usadel KH, Gale EA, Bottazzo GF. TNF-alpha gene polymorphisms in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1989;32:445–448.PubMedCrossRefGoogle Scholar
  28. 28.
    Pociot F, Briant L, Jongeneel CV, Molvig J, Worsaae H, Abbal M, Thomsen M, Nerup J, Cambon-Thomsen A. Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol 1993;23:224–231.PubMedCrossRefGoogle Scholar
  29. 29.
    Vinasco J, Beraun Y, Nieto A, Fraile A, Mataran L, Pareja E, Martin J. Polymorphism at the TNF loci in rheumatoid arthritis. Tissue Antigens 1997;49:74–78.PubMedCrossRefGoogle Scholar
  30. 30.
    Majetschak M, Flohe S, Obertacke U, Schroder J, Staubach K, Nast KD, Schade FU, Stuber F. Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg 1999;230:207–214.PubMedCrossRefGoogle Scholar
  31. 31.
    Boermeester MA, Van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995; 130:739–748.PubMedCrossRefGoogle Scholar
  32. 32.
    Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J. 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;22:396–402.PubMedCrossRefGoogle Scholar
  33. 33.
    Guasch JF, Bertina RM, Reitsma PH. Five novel intragenic dimorphisms in the human interleukin-1 genes combine to high informativity. Cytokine 1996;8:598–602.PubMedCrossRefGoogle Scholar
  34. 34.
    Reinhart K, Wiegand-Lohnert C, Grimminger F, Kaul M, Withington S, Treacher D, Eckart J, Willatts S, Bouza C, Krausch D, Stockenhuber F, Eiselstein J, Daum L, Kempeni J. Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 1996;24:733–742.PubMedCrossRefGoogle Scholar
  35. 35.
    Bowcock AM, Ray A, Erlich H, Sehgal PB. Rapid detection and sequencing of alleles in the 3′ flanking region of the interleukin-6 gene. Nucleic Acids Res 1989;17:6855–6864.PubMedCrossRefGoogle Scholar
  36. 36.
    Fugger L, Morling N, Bendtzen K, Ryder LP, Svejgaard A. BglII polymorphism in the human interleukin 6 (IL 6) gene. Nucleic Acids Res 1989;17:7548–7548.PubMedCrossRefGoogle Scholar
  37. 37.
    Fugger L, Morling N, Bendtzen K, Ryder L, Odum N, Georgsen J, Svejgaard A. Mspl polymorphism in the human interleukin 6 (IL 6) gene. Nucleic Acids Res 1989;17:4419–4419.PubMedCrossRefGoogle Scholar
  38. 38.
    Fugger L, Morling N, Bendtzen K, Ryder L, Andersen V, Heilman C, Karup Pedersen F, Friis J, Halbert P, Svejgaard A. IL-6 gene polymorphism in rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, and in healthy Danes. J Immunogenet 1989;16:461–465.PubMedCrossRefGoogle Scholar
  39. 39.
    Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996;24:1125–1128.PubMedCrossRefGoogle Scholar
  40. 40.
    Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993;91:403–404.PubMedCrossRefGoogle Scholar
  41. 41.
    Danis VA, Millington M, Hyland VJ, Grennan D. 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;99:303–310.PubMedCrossRefGoogle Scholar
  42. 42.
    Blakemore AI, Tarlow JK, Cork MJ, Gordon C, Emery P, Duff GW. Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis Rheum 1994;37:1380–1385.PubMedCrossRefGoogle Scholar
  43. 43.
    Metcalfe KA, Hitman GA, Pociot F, Bergholdt R, Tuomilehto-Wolf E, Tuomilehto J, Viswanathan M, Ramachandran A, Nerup J. An association between type 1 diabetes and the interleukin-1 receptor type 1 gene. The DiMe Study Group. Childhood Diabetes in Finland. Hum Immunol 1996;51:41–48.PubMedCrossRefGoogle Scholar
  44. 44.
    Fink MP, Payen D. The role of nitric oxide in sepsis and ARDS: synopsis of a roundtable conference held in Brussels on 18–20 March 1995. Intensive Care Med 1996;22:158–165.PubMedCrossRefGoogle Scholar
  45. 45.
    Mathiak G, Szewczyk D, Abdullah F, Ovadia P, Rabinovici R. Platelet-activating factor (PAF) in experimental and clinical sepsis. Shock. 1997;7:391–404.PubMedCrossRefGoogle Scholar
  46. 46.
    Buchman TG. Manipulation of stress gene expression: a novel therapy for the treatment of sepsis? [editorial; comment]. Crit Care Med 1994;22:901–903.PubMedCrossRefGoogle Scholar
  47. 47.
    Spitzer JA. Cytokine stimulation of nitric oxide formation and differential regulation in hepatocytes and nonparenchymal cells of endotoxemic rats. Hepatology 1994;19:217–228.PubMedCrossRefGoogle Scholar
  48. 48.
    Pfeilschifter J, Eberhardt W, Hummel R, Kunz D, Muhl H, Nitsch D, Pluss C, Walker G. Therapeutic strategies for the inhibition of inducible nitric oxide synthase-potential for a novel class of anti-inflammatory agents. Cell Biol Int 1996;20:51–58.PubMedCrossRefGoogle Scholar
  49. 49.
    Meier J, Affeldt M, Opitz C, Kleber FX, Speer A. A common base change in the promoter region of the human endothelial NO-synthase (NOS3) gene. Hum Mutat 1996;8:394–394.PubMedCrossRefGoogle Scholar
  50. 50.
    Milner CM, Campbell RD. Polymorphic analysis of the three MHC-linked HSP70 genes. Immunogenetics 1992;36:357–362.PubMedCrossRefGoogle Scholar
  51. 51.
    Pociot F, Ronningen KS, Nerup J. Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70-2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM). Scand J Immunol 1993;38:491–495.PubMedCrossRefGoogle Scholar
  52. 52.
    Janeway-CA J, Medzhitov R. Lipoproteins take their toll on the host. Curr Biol 1999;9:R879–R882.PubMedCrossRefGoogle Scholar
  53. 53.
    Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi CP, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998;282:2085–2088.PubMedCrossRefGoogle Scholar
  54. 54.
    Takeuchi O, Kawai T, Sanjo H, Copeland NG, Gilbert DJ, Jenkins NA, Takeda K, Akira S. TLR6: A novel member of an expanding toll-like receptor family. Gene 1999;231:59–65.PubMedCrossRefGoogle Scholar
  55. 55.
    Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ. Peptidoglycan-and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 1999;274:17406–17409.PubMedCrossRefGoogle Scholar
  56. 56.
    Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol 1999; 163:1–5.PubMedGoogle Scholar
  57. 57.
    Takeuchi O, Kaufmann A, Grote K, Kawai T, Hoshino K, Morr M, Muhlradt PF, Akira S. Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2-and MyD88-dependent signaling pathway. J Immunol 2000;164:554–557.PubMedGoogle Scholar
  58. 58.
    Poltorak A, Smirnova I, He X, Liu MY, Van-Huffel C, McNally O, Birdwell D, Alejos E, Silva M, Du X, Thompson P, Chan EK, Ledesma J, Roe B, Clifton S, Vogel SN, Beutler B. Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 1998;24:340–355.PubMedCrossRefGoogle Scholar
  59. 59.
    Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 1999; 11:443–451.PubMedCrossRefGoogle Scholar
  60. 60.
    Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 2000;164:558–561.PubMedGoogle Scholar
  61. 61.
    Cario E, Rosenberg IM, Brandwein SL, Beck PL, Reinecker HC, Podolsky DK. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J Immunol 2000; 164:966–972.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Frank Stüber
    • 1
  1. 1.Department of Anesthesiology and Critical Care MedicineUniversity of BonnBonnGermany

Personalised recommendations