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15 January 2007

Volume 195, Number 2
The Journal of Infectious Diseases 2007;195:288–295
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19502-0017$15.00
DOI: 10.1086/510313
MAJOR ARTICLE

Th2 Cytokines Are Associated with Persistent Hepatic Fibrosis in Human Schistosoma japonicum Infection

H. M. Coutinho,1,3

L. P. Acosta,7

H. W. Wu,1

S. T. McGarvey,2,3

L. Su,4

G. C. Langdon,1

M. A. Jiz,7

B. Jarilla,7

R. M. Olveda,7

J. F. Friedman,1,5 and

J. D. Kurtis1,6

1Center for International Health Research, Rhode Island Hospital, and 2Epidemiology Section, 3Department of Community Health and International Health Institute, and 4Center for Statistical Sciences, Brown University, and Departments of 5Pediatrics and 6Pathology and Laboratory Medicine, Brown University Medical School, Providence, Rhode Island; 7Research Institute of Tropical Medicine, Manila, the Philippines

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum–infected participants 7–30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]–4, IL‐5, IL‐10, IL‐13, tumor necrosis factor–α, and interferon‐γ) produced by peripheral‐blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL‐4 to SWAP and IL‐10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables ( , for all). In participants with fibrosis at baseline, IL‐4 to SWAP and IL‐5 and IL‐13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment ( , for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females ( , for all). These results suggest an independent role for Th2‐biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male‐biased prevalence of fibrosis.

Received 11 June 2006; accepted 11 September 2006; electronically published 13 December 2006.

Reprints or correspondence: Dr. Hannah M. Coutinho, Center for International Health Research, Rhode Island Hospital, Brown University Medical School, 55 Claverick St., Box 3, Providence, RI 02903 ( or ).

Cited by

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M. L. BURKE, M. K. JONES, G. N. GOBERT, Y. S. LI, M. K. ELLIS, D. P. McMANUS. (2009) Immunopathogenesis of human schistosomiasis. Parasite Immunology 31:4, 163-176
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M. Y. Elsammak, R. M. Al-Sharkaweey, M. S. Ragab, G. M. Amin, M. H. Kandil. (2009) In Egyptians, a mutation in the lymphotoxin-α gene may increase susceptibility to hepatitis C virus but not that to schistosomal infection. Annals of Tropical Medicine and Parasitology 102:8, 709-716
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Violaine Arnaud, Jun Li, Yuanyuan Wang, Xiao Fu, Shi Mengzhi, Xinsong Luo, Xunya Hou, Helia Dessein, Zhou Jie, Yu Xin‐Ling, Hongbin He, Donald P. McManus, Yuesheng Li, and Alain Dessein. (2008) Regulatory Role of Interleukin–10 and Interferon-γ in Severe Hepatic Central and Peripheral Fibrosis in Humans Infected with Schistosoma japonicum. The Journal of Infectious Diseases 198:3, 418-426
Online publication date: 1-Aug-2008.
Abstract-Full Text-PDF Version (236 kB)

  • Potential conflicts of interest: none reported.

    Financial support: National Institutes of Health (grants R01AI48123 and K23AI52125).

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