Role of IL-8, IL-10 and TNF-α level in pathogenesis of leptospiral acute hepatitis syndrome
Keywords:
Leptospirosis, Cytokines, ELISA, Immunopathogenesis, Hepatitis, Interleukins, TNF,
Abstract
Background: Leptospirosis is the most widespread zoonosis occurring worldwide. Severity of disease may range from inapparent infection to fulminant, fatal disease. Besides, direct injury by microbial factors, cytokines produced in response to infection have been proposed to be involved in the pathogenesis of leptospirosis.Objective: This study was done to assess the impact of cytokines IL-8, IL-10 and TNF-α in pathogenesis of leptospirosis and to establish their role as diagnostic markers in disease severity.Methods: Fourty six patients with signs and symptoms of acute hepatitis who were positive for leptospira by IgM ELISA along with 30 control individuals were included in the study. Concentrations of circulating IL-8, IL-10 & TNF-α were measured in pg/ml by ELISA.Results: There were two to threefold rise in liver enzymes in patients with leptospirosis. Concentrations of IL-8, IL-10 were found to be elevated in 41 (89.1%), 26 (56.52%) patients while that of TNF-α were largely suppressed in patients with leptospirosis. Mean levels of IL-8, IL-10 & TNF-α was 175.96 pg/ml, 32.9 pg/ml and 46.49 pg/ml respectively. Higher levels of IL-8, IL-10 and lower levels of TNF-α were found to be associated with better prognosis. IL-10/TNF-α ratio was significantly high in our study.Conclusion: Ratios of IL-10/TNF-α may play a role in predicting disease prognosis as high IL-10/TNF-α ratios are associated with good prognosis.References
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21) de Fost M, Hartskeerl RA, Groenendijk MR, vander Poll T. Interleukin 12 in part regulates gamma interferon releasein human whole blood stimulated with Leptospira interrogans. Clinical and Diagnostic Laboratory Immunology. 2003;10:332–5.
22) Bozkaya H, Bozdayi M, Turkyilmaz R, Sarioglu M, Cetinkaya H, Cinar K, et al. Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: their relations to HBeAg status and the activity of liver disease. Journal of Hepatogastroenterology. 2000;47:1675-9.
23) Adib-Conquy M, Moine P, Asehnoune K, Edouard A, Espevik T, Miyake K, et al. Toll-like receptor-mediated tumor necrosis factor and interleukin-10 production differ during systemic inflammation. Am. J. Respir. Crit. Care Med. 2003;168:158-64.
24) Frédérique VP, Fabrice M. Proinflammatory and Immunomodulatory Cytokine mRNA Time Course Profiles in Hamsters Infected with a Virulent Variant of Leptospira inter-rogans. Infect Immun. 2006;74: 4172–9.
25) Woranart J, Chantiwa W, Suwanna N, Su-wimol T, Nawarat C. Wara-aswapati, et al. Differential Response of Cytokines In-duced by Leptospira interrogans, Sero-group Pomona, Serovar Pomona, in Mouse and Human Cell Lines. Asian Pacific Journal of Allergy and Immunology. 2008;26: 229-35.
2) Rizvi M, Azam, Ajmal MR, Shukla I, Malik A. Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral Hepatitis. Annals of tropical medicine & parasitology. 2011;105:499–506.
3) Levett PN, Branch SL, Edwards CN. Detection of dengue infection in patients investigated for leptospirosis in Barbados. Am Journal of Trop Med and Hygiene. 2000;62:112–4.
4) Flannery B, Pereira MM, Velloso L de F, Carvalho C de C, De Codes L G, Orrico G de S, et al. Referral pattern of leptospirosis cases during a large urban epidemic of dengue. Am Journal of Trop Med and Hygiene. 2001;65: 657–63.
5) LaRocque RC, Breiman RF, Ari MD, Morey RE, Janan FA, Hayes JM, et al. Leptospirosis during dengue outbreak, Bangladesh. Emerging Infectious Diseases. 2005;11:766–9.
6) Bharadwaj R, Bal AM, Joshi SA, Kagal A, Pol SS, Garad G, et al. An urban outbreak of leptospirosis in Mumbai, India. Japanese Journal of Inf Dis. 2002;55:194–6.
7) Sambasiva RR, Naveen G, Bhalla P, Agarwal SK. Leptospirosis in India and rest of the world. Brazilian Journal of Infectious Diseases; 2003;7:178–93.
8) Luzia SC, Roberto V, Antonio AL. Leptospirosis: a worldwide resurgent zoonosis and important cause of acute renal failure and death in developing nations. Ethnicity & Disease; 2009;19:37–41.
9) Chin J ed. Leptospirosis. In: Control of Communicable Diseases Manual 17th ed. American Public Health Association, Washington. 2000;293–6.
10) Lowanichapat A, Payungporn S, Sereemaspun A, Ekpo P, Phulsuksombati, Poovorawan Y, et al. Expression of TNF-α, TGF-β, IP-10 and IL-10 mRNA in kidneys of hamsters infected with pathogenic Leptospira. Comp Immunol Microbiol Infect Dis. 2009;714-26.
11) Cohen J. The immunopathogenesis of sepsis. Nature. 2002;420: 885–91.
12) Tajiki H, Salomao R. Association of plasma levels of tumor necrosis factor alpha with severity of disease and mortality among patients with leptospirosis. Clin. Infect. Dis. 1996;23:1177-8.
13) Al-Ashy R, Chakroun I, El-Sabban ME, Homaidan FR. The role of NF kappa B in mediating the anti-inflammatory effects of IL-10 in intestinal epithelial cells. Cytokine. 2006;36: 1–8.
14) van Dissel JT, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet. 1998;351: 950–3.
15) Kyriakidis I, Samara P, Papa A. Serum TNF-a, sTNFR1, IL-6, IL-8 and IL-10 levels in Weil’s syndrome. Cytokine. 2011;54, 117–20.
16) Wagenaar JFP, Goris MGA, Gasem MH, Isbandrio B, Moalli F, Mantovani A, et al. Long pentraxin PTX3 is associated with mortality and disease severity in severe leptospirosis. Journal of Infection. 2009;58:425–32.
17) Christou L, Kalambokis G, Tsianos EV. Weil’s disease in a patient with chronic viral hepatitis and history of alcohol abuse. Internal Medicine. 2008;47:933–7.
18) Everard JD, Everard COR. Leptospirosis in the Caribbean. Rev Med Microbiol. 1993;4: 114-22.
19) Barua HC, Biswas D, Mahanta J. Regional Medical Research Centre, NE Region (ICMR), Assam. Clinico-epidemiological study on leptospirosis in certain parts of north-eastern region. J Commun Dis. 1999;31: 201-2.
20) Manocha H, Ghoshal U, Singh SK, Kishore J, Ayyagari A. Frequency of Leptospirosis in Patients of Acute Febrile Illness in Uttar Pradesh. J Assoc Physic India. 2004;52:623-5.
21) de Fost M, Hartskeerl RA, Groenendijk MR, vander Poll T. Interleukin 12 in part regulates gamma interferon releasein human whole blood stimulated with Leptospira interrogans. Clinical and Diagnostic Laboratory Immunology. 2003;10:332–5.
22) Bozkaya H, Bozdayi M, Turkyilmaz R, Sarioglu M, Cetinkaya H, Cinar K, et al. Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: their relations to HBeAg status and the activity of liver disease. Journal of Hepatogastroenterology. 2000;47:1675-9.
23) Adib-Conquy M, Moine P, Asehnoune K, Edouard A, Espevik T, Miyake K, et al. Toll-like receptor-mediated tumor necrosis factor and interleukin-10 production differ during systemic inflammation. Am. J. Respir. Crit. Care Med. 2003;168:158-64.
24) Frédérique VP, Fabrice M. Proinflammatory and Immunomodulatory Cytokine mRNA Time Course Profiles in Hamsters Infected with a Virulent Variant of Leptospira inter-rogans. Infect Immun. 2006;74: 4172–9.
25) Woranart J, Chantiwa W, Suwanna N, Su-wimol T, Nawarat C. Wara-aswapati, et al. Differential Response of Cytokines In-duced by Leptospira interrogans, Sero-group Pomona, Serovar Pomona, in Mouse and Human Cell Lines. Asian Pacific Journal of Allergy and Immunology. 2008;26: 229-35.
Published
2014-09-28
Section
Original Article
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