Yıl 2018,
Cilt: 35 Sayı: 1, 30 - 35, 01.01.2018
Leyla Acar
Nazan Atalan
E. Hande Karagedik
Arzu Ergen
Kaynakça
- 1. Hotchkiss RS, Karl IE. The Pathophysiology and treatment of sepsis. N
Engl J Med 2003;348:138-50.
- 2. Karban AS, Okazaki T, Panhuysen CI, Gallegos T, Potter JJ, Bailey-Wilson
JE, et al. Functional annotation of a novel NFKB1 promoter polymorphism
that increases risk for ulcerative colitis. Hum Mol Genet 2004;13:35-45.
- 3. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and
IKK function. Nat Rev Mol Cell Biol 2007;8:49-62.
- 4. Chen F, Castranova V, Shi X, Demers LM. New insights into the role of
nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of
diseases. Clin Chem 1999;45:7-17.
- 5. Schäfer ST, Gessner S, Scherag A, Rump K, Frey UH, Siffert W, et al.
Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in
deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/
delATTG) and is associated with increased 30-day mortality in septic
shock. PLoS One 2014;9:e104953.
- 6. Reinhart K, Karzai W. Anti-tumor necrosis factor therapy in sepsis: update
on clinical trials and lessons learned. Crit Care Med 2001;29:121-5.
- 7. Feezor RJ, Oberholzer C, Baker HV, Novick D, Rubinstein M, Moldawer LL, et
al. Molecular characterization of the acute inflammatory response to infections
with gram-negative versus gram-positive bacteria. Infect Immun 2003;5803-13.
- 8. Pujhari SK, Ratho RK, Prabhakar S, Mishra B, Modi M. TNF-α promoter
polymorphism: a factor contributing to the different immunological and
clinical phenotypes in Japanese encephalitis. BMC Infect Dis 2012;12:23.
- 9. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns
D, Huber-Lang M, et al. Sepsis induced changes of adipokines and
cytokines - septic patients compared to morbidly obese patients. BMC Surg
2010;10:26.
- 10. Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, et al.
Association of TNF2, a TNF-alpha promoter polymorphism, with
septic shock susceptibility and mortality: a multicenter study. JAMA
1999;282:561-8.
- 11. Appoloni O, Dupont E, Vandercruys M, Andriens M, Duchateau J, Vincent
JL. Association of tumor necrosis factor-2 allele with plasma tumor
necrosis factor-alpha levels and mortality from septic shock. Am J Med
2001;110:486-488.
- 12. Louis E, Franchimont D, Piron A, Gevaert Y, Schaaf-Lafontaine N, Roland
S, et al. Tumour necrosis factor (TNF) gene polymorphism influences
TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole
blood cell culture in healthy humans. Clin Exp Immunol 1998;113:401-
6.
- 13. Zhang M, Zhao Y, Liu Q. Tumor necrosis factor-α -308G/A and -238G/A
polymorphisms are associated with increased risks of sepsis: evidence
from an updated meta-analysis. APMIS 2017;125:459-67.
- 14. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et
al. Definitions for sepsis and organ failure and guidelines for the use of
innovative therapies in sepsis. The ACCP/SCCM Consensus Conference
Committee. American College of Chest Physicians/Society of Critical Care
Medicine. Chest 1992;101:1644-55.
- 15. Goldstein B, Giroir B, Randolph A; International Consensus Conference
on Pediatric Sepsis. International pediatric sepsis consensus conference:
definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care
Med 2005;6:2-8.
- 16. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, LopezRodriguez
A, et al. Efficacy and safety of recombinant human activated
protein C for severe sepsis. N Eng J Med 2001;344:699-709.
- 17. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest 2000;117:1162-
72.
- 18. O'Dwyer MJ, Mankan AK, Stordeur P, O'Connell B, Duggan E, White M.
The occurrence of severe sepsis and septic shock are related to distinct
patterns of cytokine gene expression. Shock 2006;26:544-50.
- 19. Srinivasan L, Page G, Kirpalani H, Murray JC, Das A, Higgins RD, et al.
Genome-wide association study of sepsis in extremely premature infants.
Arch Dis Child Fetal Neonatal Ed 2017;102:439-45.
- 20. Somech R, Amariglio N, Spirer Z, Rechavi G. Genetic predisposition to
infectious pathogens: a review of less familiar variants. Pediatr Infect Dis J
2003;22:457-61.
- 21. Emonts M, Hazelzet JA, de Groot R, Hermans PW. Host genetic
determinants of Neisseria meningitidis infections. Lancet Infect Dis
2003;3:565-77.
- 22. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J
Clin Invest 2001;107:7-11.
- 23. Gökay SS, Yıldızdaş RD, Yılmaz M, Aksoy K, Yalın AE, Sertdemir Y, et al.
MyD 88 Polymorphisms in Children Diagnosed with Sepsis. Balkan Med J
2016;33:633-8.
- 24. Giachelia M, Voso MT, Tisi MC, Martini M, Bozzoli V, Massini G, et al.
Interleukin-6 plasma levels are modulated by a polymorphism in the NFκB1
gene and are associated with outcome following rituximab-combined
chemotherapy in diffuse large B-cell non-Hodgkin lymphoma. Leuk
Lymphoma 2012;53:411-6.
- 25. Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton
JW. TLR4 and TNF-alpha polymorphisms are associated with an increased
risk for severe sepsis following burn injury. J Med Genet 2004;41:808-13.
- 26. Song Z, Song Y, Yin J, Shen Y, Yao C, Sun Z, et al. Genetic variation in the
TNF gene is associated with susceptibility to severe sepsis, but not with
mortality. PLoS One 2012;7:46113.
- 27. Feng B, Mao ZR, Pang K, Zhang SL, Li L. Association of tumor necrosis
factor α -308G/A and interleukin-6 -174G/C gene polymorphism with
pneumonia-induced sepsis. J Crit Care 2015;30:920-3.
- 28. Baghel K, Srivastava RN, Chandra A, Goel SK, Agrawal J, Kazmi HR, et
al. TNF-α, IL-6, and IL-8 cytokines and their association with TNF-α-308
G/A polymorphism and postoperative sepsis. J Gastrointest Surg
2014;18:1486-94.
- 29. de Bont ES, Martens A, van Raan J, Samson G, Fetter WP, Okken A, et al.
Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma
levels in neonatal sepsis. Pediatr Res 1993;33:380-3.
- 30. Ozdemir A, Oygür N, Gültekin M, Coşkun M, Yeğin O. Neonatal tumor
necrosis factor, interleukin-1 alpha, interleukin-1 beta, and interleukin-6
response to infection. Am J Perinatol 1994;11:282-5.
- 31. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels
correlate with survival in patients with the sepsis syndrome. Ann Intern
Med 1993;119:771-8.
- 32. van Deuren M, van der Ven-Jongekrijg J, Demacker PN, Bartelink AK, van
Dalen R, Sauerwein RW, et al. Differential expression of proinflammatory
cytokines and their inhibitors during the course of meningococcal
infections. J Infect Dis 1994;169:157-61.
- 33. Kothari N, Bogra J, Abbas H, Kohli M, Malik A, Kothari D, et al. Tumor
necrosis factor gene polymorphism results in high TNF level in sepsis and
septic shock. Cytokine 2013;61:676-81.
- 34. Bavunoglu I, Genc H, Konukoglu D, Cicekci H, Sozer V, Gelisgen R, et al.
Oxidative stress parameters and inflammatory and immune mediators as
markers of the severity of sepsis. J Infect Dev Ctries 2016;10:1045-52.
- 35. Butt C, Sun S, Peddle L, Greenwood C, Hamilton S, Gladman D, et al.
Association of nuclear factor-kappaB in psoriatic arthritis. J Rheumatol
2005;32:1742-4.
- 36. Borm ME, van Bodegraven AA, Mulder CJ, Kraal G, Bouma G. A NFKB1
promoter polymorphism is involved in susceptibility to ulcerative colitis.
Int J Immunogenet 2005;32:401-5.
- 37. Adamzik M, Schäfer S, Frey UH, Becker A, Kreuzer M, Winning S, et al. The NFKB1 promoter polymorphism (-94ins/delATTG) alters nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation and is associated with increased mortality in sepsis. Anesthesiology 2013;118:123-33.
Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis
Yıl 2018,
Cilt: 35 Sayı: 1, 30 - 35, 01.01.2018
Leyla Acar
Nazan Atalan
E. Hande Karagedik
Arzu Ergen
Öz
Background: The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. Aims: To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Study Design: Case-control study. Methods: Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction–restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. Results: We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Conclusion: Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.
Kaynakça
- 1. Hotchkiss RS, Karl IE. The Pathophysiology and treatment of sepsis. N
Engl J Med 2003;348:138-50.
- 2. Karban AS, Okazaki T, Panhuysen CI, Gallegos T, Potter JJ, Bailey-Wilson
JE, et al. Functional annotation of a novel NFKB1 promoter polymorphism
that increases risk for ulcerative colitis. Hum Mol Genet 2004;13:35-45.
- 3. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and
IKK function. Nat Rev Mol Cell Biol 2007;8:49-62.
- 4. Chen F, Castranova V, Shi X, Demers LM. New insights into the role of
nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of
diseases. Clin Chem 1999;45:7-17.
- 5. Schäfer ST, Gessner S, Scherag A, Rump K, Frey UH, Siffert W, et al.
Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in
deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/
delATTG) and is associated with increased 30-day mortality in septic
shock. PLoS One 2014;9:e104953.
- 6. Reinhart K, Karzai W. Anti-tumor necrosis factor therapy in sepsis: update
on clinical trials and lessons learned. Crit Care Med 2001;29:121-5.
- 7. Feezor RJ, Oberholzer C, Baker HV, Novick D, Rubinstein M, Moldawer LL, et
al. Molecular characterization of the acute inflammatory response to infections
with gram-negative versus gram-positive bacteria. Infect Immun 2003;5803-13.
- 8. Pujhari SK, Ratho RK, Prabhakar S, Mishra B, Modi M. TNF-α promoter
polymorphism: a factor contributing to the different immunological and
clinical phenotypes in Japanese encephalitis. BMC Infect Dis 2012;12:23.
- 9. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns
D, Huber-Lang M, et al. Sepsis induced changes of adipokines and
cytokines - septic patients compared to morbidly obese patients. BMC Surg
2010;10:26.
- 10. Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, et al.
Association of TNF2, a TNF-alpha promoter polymorphism, with
septic shock susceptibility and mortality: a multicenter study. JAMA
1999;282:561-8.
- 11. Appoloni O, Dupont E, Vandercruys M, Andriens M, Duchateau J, Vincent
JL. Association of tumor necrosis factor-2 allele with plasma tumor
necrosis factor-alpha levels and mortality from septic shock. Am J Med
2001;110:486-488.
- 12. Louis E, Franchimont D, Piron A, Gevaert Y, Schaaf-Lafontaine N, Roland
S, et al. Tumour necrosis factor (TNF) gene polymorphism influences
TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole
blood cell culture in healthy humans. Clin Exp Immunol 1998;113:401-
6.
- 13. Zhang M, Zhao Y, Liu Q. Tumor necrosis factor-α -308G/A and -238G/A
polymorphisms are associated with increased risks of sepsis: evidence
from an updated meta-analysis. APMIS 2017;125:459-67.
- 14. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et
al. Definitions for sepsis and organ failure and guidelines for the use of
innovative therapies in sepsis. The ACCP/SCCM Consensus Conference
Committee. American College of Chest Physicians/Society of Critical Care
Medicine. Chest 1992;101:1644-55.
- 15. Goldstein B, Giroir B, Randolph A; International Consensus Conference
on Pediatric Sepsis. International pediatric sepsis consensus conference:
definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care
Med 2005;6:2-8.
- 16. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, LopezRodriguez
A, et al. Efficacy and safety of recombinant human activated
protein C for severe sepsis. N Eng J Med 2001;344:699-709.
- 17. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest 2000;117:1162-
72.
- 18. O'Dwyer MJ, Mankan AK, Stordeur P, O'Connell B, Duggan E, White M.
The occurrence of severe sepsis and septic shock are related to distinct
patterns of cytokine gene expression. Shock 2006;26:544-50.
- 19. Srinivasan L, Page G, Kirpalani H, Murray JC, Das A, Higgins RD, et al.
Genome-wide association study of sepsis in extremely premature infants.
Arch Dis Child Fetal Neonatal Ed 2017;102:439-45.
- 20. Somech R, Amariglio N, Spirer Z, Rechavi G. Genetic predisposition to
infectious pathogens: a review of less familiar variants. Pediatr Infect Dis J
2003;22:457-61.
- 21. Emonts M, Hazelzet JA, de Groot R, Hermans PW. Host genetic
determinants of Neisseria meningitidis infections. Lancet Infect Dis
2003;3:565-77.
- 22. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J
Clin Invest 2001;107:7-11.
- 23. Gökay SS, Yıldızdaş RD, Yılmaz M, Aksoy K, Yalın AE, Sertdemir Y, et al.
MyD 88 Polymorphisms in Children Diagnosed with Sepsis. Balkan Med J
2016;33:633-8.
- 24. Giachelia M, Voso MT, Tisi MC, Martini M, Bozzoli V, Massini G, et al.
Interleukin-6 plasma levels are modulated by a polymorphism in the NFκB1
gene and are associated with outcome following rituximab-combined
chemotherapy in diffuse large B-cell non-Hodgkin lymphoma. Leuk
Lymphoma 2012;53:411-6.
- 25. Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton
JW. TLR4 and TNF-alpha polymorphisms are associated with an increased
risk for severe sepsis following burn injury. J Med Genet 2004;41:808-13.
- 26. Song Z, Song Y, Yin J, Shen Y, Yao C, Sun Z, et al. Genetic variation in the
TNF gene is associated with susceptibility to severe sepsis, but not with
mortality. PLoS One 2012;7:46113.
- 27. Feng B, Mao ZR, Pang K, Zhang SL, Li L. Association of tumor necrosis
factor α -308G/A and interleukin-6 -174G/C gene polymorphism with
pneumonia-induced sepsis. J Crit Care 2015;30:920-3.
- 28. Baghel K, Srivastava RN, Chandra A, Goel SK, Agrawal J, Kazmi HR, et
al. TNF-α, IL-6, and IL-8 cytokines and their association with TNF-α-308
G/A polymorphism and postoperative sepsis. J Gastrointest Surg
2014;18:1486-94.
- 29. de Bont ES, Martens A, van Raan J, Samson G, Fetter WP, Okken A, et al.
Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma
levels in neonatal sepsis. Pediatr Res 1993;33:380-3.
- 30. Ozdemir A, Oygür N, Gültekin M, Coşkun M, Yeğin O. Neonatal tumor
necrosis factor, interleukin-1 alpha, interleukin-1 beta, and interleukin-6
response to infection. Am J Perinatol 1994;11:282-5.
- 31. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels
correlate with survival in patients with the sepsis syndrome. Ann Intern
Med 1993;119:771-8.
- 32. van Deuren M, van der Ven-Jongekrijg J, Demacker PN, Bartelink AK, van
Dalen R, Sauerwein RW, et al. Differential expression of proinflammatory
cytokines and their inhibitors during the course of meningococcal
infections. J Infect Dis 1994;169:157-61.
- 33. Kothari N, Bogra J, Abbas H, Kohli M, Malik A, Kothari D, et al. Tumor
necrosis factor gene polymorphism results in high TNF level in sepsis and
septic shock. Cytokine 2013;61:676-81.
- 34. Bavunoglu I, Genc H, Konukoglu D, Cicekci H, Sozer V, Gelisgen R, et al.
Oxidative stress parameters and inflammatory and immune mediators as
markers of the severity of sepsis. J Infect Dev Ctries 2016;10:1045-52.
- 35. Butt C, Sun S, Peddle L, Greenwood C, Hamilton S, Gladman D, et al.
Association of nuclear factor-kappaB in psoriatic arthritis. J Rheumatol
2005;32:1742-4.
- 36. Borm ME, van Bodegraven AA, Mulder CJ, Kraal G, Bouma G. A NFKB1
promoter polymorphism is involved in susceptibility to ulcerative colitis.
Int J Immunogenet 2005;32:401-5.
- 37. Adamzik M, Schäfer S, Frey UH, Becker A, Kreuzer M, Winning S, et al. The NFKB1 promoter polymorphism (-94ins/delATTG) alters nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation and is associated with increased mortality in sepsis. Anesthesiology 2013;118:123-33.