Production of tumor necrosis factor-a is increased in urinary tract infections

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Neni Susilaningsih
Bambang Joni Karjono
Ratna Damma Purnamawati


BACKGROUND Urinary tract infection (UTI) is a common source of bacteriemia. The most common cause of UTI is Escherichia coli (E. coli). Tumor Necrosis Factor (TNF)-á gene polymorphism has been reported to be responsible for an excessive production of TNF-á and eventual disruption of pro-inflammatory cytokine regulation. The aim of this study was to compare TNF-á serum levels and TNF-á allele polymorphisms in patients with UTI due to E.coli and in non- UTI controls. METHODS A cross-sectional study was conducted at Dr. Kariadi Central Hospital and the Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang. In 68 patients with UTI the TNF-á serum levels were determined by means of ELISA and compared to those of non-UTI controls (n=55). TNFá- 308G>A gene polymorphism was analyzed by polymerase chain reaction restriction fragment length using the NcoI enzyme. Fragments were visualized on polyacrylamide gel with silver staining. RESULTS TNF-á serum level in patients with UTI had a median of 8.9 pg/mL, which was significantly higher than the median of 3.7 pg/mL in the control group (pA gene polymorphisms found in the patient group were G/G=61 (90%), G/A=7(10%) and A/A=0, while in the control group were G/G=48 (87%), G/A=7 (13%) and A/A =0. There was no significant differences (p=0.578) in gene polymorphisms between the two groups. CONCLUSIONS TNF-á serum levels in patients with UTI due to E. coli were significantly higher than in non-UTI controls, but for the TNF-á-380 gene polymorphisms no significant difference was found between the two groups. There are presumably more important factors than host genotype that influence UTI pathogenesis.

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Susilaningsih, N., Karjono, B. J., & Purnamawati, R. D. (2012). Production of tumor necrosis factor-a is increased in urinary tract infections. Universa Medicina, 31(3), 167–174.
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Salvatore S, Salvatore S, Cattoni E, Siesto G, Serati M, Sorice P, et al. Urinary tract infections in women. Eur J Obstet Gynecol Reprod Biol 2011;156:131-6.

Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis Urol Clin North Am 2008;35:1–12.

Bingen-Bidois M, Clermont O, Bonacorsi S, Terki M, Brahimi N, Loukil C, et al. Phylogenetics analysis and prevalence of

urosepsis strain of Escherechia coli bearing phatogenecity island like-domains. Infect Immun 2002;70:3216-26.

Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med 2002;113 Suppl 1A:S14–9.

Nicolle LE. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol 2005;16:349-60.

Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens Dis Mon 2003;49:71–82.

Lee S-J, Kim SW, Cho Y-H, Yoon MS. Antiinflammatory effect of an Escherichia coli extract in a mouse model of lipopolysaccharide-induced cystitis. World J Urol 2006;24:33-8.

Kucheria R, Dasgupta P, Sacks SH, Khan MS, Sheerin NS. Urinary tract infections: new insights into a common problem. Postgrad Med J 2005;81:83-6.

Ramesh G, Kimball SR, Jefferson LS, Reeves WB. Endotoxin and cisplatin synergistically stimulate TNF- production by renal epithelial cells. Am J Physiol Renal Physiol 2007;292:F812–9.

Mohkam M, Asgarian F, Fahimzad A, Sharifian M, Dalirani R, Gorgi FA. Diagnostic potential of urinary tumor necrosis factor-alpha in children with acute pyelonephritis. Iranian J Kidney Dis 2009;3:89-92.

Wong HR. Genetics and genomics in pediatric septic shock. Crit Care Med 2012;40:1618-26.

Knuefermann P, Remoto S, Baumgarten G, Misra A, Sivasubramanian N, Carabello B, et al. Cardiac inflammation and innate immunity in septic shock. Is there a role for toll like receptors? Chest 2002;121:1329-36.

Holmes CL, Russell JA, Walley KR. Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy. Chest 2003;124:1103-15.

Hotchkiss R, Karl I. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138-50.

Sipahi T, Pocan H, Akar N. Efect of various genetic polymorphisms on the incidence and outcome of sever sepsis. Clin Appl Thromb Hemost 2006;12:47-54.

Mossböck G, Renner W, El-Shabrawi Y, Faschinger C, Schmut O, Wedrich A, et al. TNFá –308 G>A and –238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma. Mol Vis 2009;15:518-22.

Haukim N, Bidwell J, AJP AJPS, Keen LJ, Gallagher G, Kimberly R, et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 2. Genes Immun 2002;3:


Hollegaard M, Bidwell J. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 2006;7 Suppl 3:S269–76.

Ngestiningsih D, Faradz SMH. Polimorfisme Alel TNF-alfa pada penderita DHF di Semarang. M Med Indones 2006;41:46-51.

Moukoko CE, El-Wali N, Saeed OK, Mohamed- Ali Q, Gaudart J, Dessein AJ, et al. No evidence for a major effect of tumor necrosis factor alpha gene polymorphisms in periportal fibrosis caused by Schistosomamansoni infection. Infect Immun


Knuefermann P, Remoto S, Baumgarten G, Misra A, Sivasubramanian N, Aabello BA, et al. Cardiac inflammation and innate immunity in septic shock. Is there a role for toll like receptors? Chest 2002;121:1329-36.

Svanborg C, Bergsten G, Fischer H, Godaly G, Gustafsson M, Karpman D, et al. Uropathogenic Escherichia coli as a model of host-parasite interaction. Curr Opin Microbiol 2006;9:33-9.

Engel D, Dobrindt U, Tittel A, Peters P, Maurer J, Gutgemann I, et al. Tumor necrosis factor alpha- and inducible nitric oxide synthaseproducing dendritic cells are rapidly recruited

to the bladder in urinary tract infection but are dispensable for bacterial clearance. Infect Immun 2006;74:6100-7.

Sadeghi M, Daniel V, Naujokat C, Wiesel M, Hergesell O, Opelz G. Strong inflammatory cytokine response in male and strong antiinflammatory response in female kidney

transplant recipients with urinary tract infection. Transpl Int 2005;18:177-85.

Sallakci N, Akcurin G, Koksoy S, Kardelen F, Uguz A, Coskun M, et al. TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha

production. J Autoimmun 2005;25:150-4.

Krasowska D, Chodorowska G, Koziol- Montewka M, Ksiazek A, Buraczynska M. The -308 promoter polymorphism in the tumour necrosis factor gene in patients with lichen

planus. Acta Derm Venereol 2005;85:400-3.

Moffett S, Zmuda J, Oakley J, Beck T, Cauley J, Stone K, et al. Tumor necrosis factor- á polymorphism, bone strength phenotypes, and the risk of fracture in older women. J Clin

Endocrinol Metab 2005;90:3491–7.

Cabantou S, Doumbo O, Ranque S, Poudiougou B, Traore A, Hou X, et al. Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not increase the risk of severe malaria in

children with Plasmodium falciparum infection in Mali. Infect Immun 2006;74:7040–2.