Alexandria Journal of Pediatrics, Volume 16, Number 2, July 2002 327 Elevated Levels of Interleukin 18 in Children with Acute and Chronic Liver Disease: Further Evidence of T Cell-Mediated Liver Injury Magd A. Kotb, 1 Amira Idrees, 1 Wael N. Lotfi, 1 Gamal Taha, 2 and Mona Aziz 3 From the departments of Pediatrics, Cairo University, 1 Pediatrics, Cairo University-Banisoef Branch, 2 and Clinical Pathology, Cairo University, Egypt Abstract: IL-18, derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. The objective of this study was to evaluate IL-18 in sera of infants and children suffering from acute hepatitis, chronic hepatitis and cirrhosis and to define its role as a predictive factor for chronicity of liver disease. Eighteen children suffering from acute viral hepatitis, 26 from chronic hepatitis and 15 suffering from cirrhosis were included in this study. They were attendants of the Hepatology Clinic of the New Children’s Hospital, Cairo University. Twenty-three age and sex matched, clinically free infants and children, were also included as a control group. All studied infants and children, and the control group underwent quantitative determination of IL-18 in serum by ELISA. The mean IL-18 was found to be statistically significantly lower among the control group compared to the others. The mean IL-18 values were 38.65+ 15.46, 510.27+ 757, 305.03+ 647 and 257.86+ 395 pg/ml for the healthy control, acute hepatitis, chronic hepatitis and cirrhosis groups respectively. IL-18 level was not found to be predictive of pathology or etiology (P=0.067). No correlation was found between IL-18 level and total bilirubin (P=0.70), direct bilirubin (P=0.79), ALT (P=0.29), AST (P=0.48) or alkaline phosphatase (P=0.222). Higher levels of IL-18 were encountered in those children having more severe AIH. Conclusion : High IL-18 was present in children having various liver diseases. This supports the view that hepatocytes destruction is in part immune mediated. Immune modulation remains a potential future perspective for liver disease intervention. Introduction: Cytokines are pleiotropic regulatory peptides that can be produced by virtually every nucleated cell in the body, including most types of liver cells. The cytokine family consists of several subfamilies as the interleukins, the tumour necrosis factor (TNF) family. 1 Interleukin 18 (IL-18) is a product of activated macrophages (including Kupffer cells) and, with IL-12, induces interferon γ production from T cells. 2 IL-18 has a variety of biologic effects consistent with its role in promoting Th1 cell clone development. 3 IL-18, derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. 4 In most tissues, including the liver, constitutive production of cytokines is absent or minimal. However, as physiologic and pathologic stimuli activate cells, the production of these autocrine, paracrine, and endocrine effector molecules increases, and they, in turn, orchestrate the tissue's response to the stimulus. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis, and fibrosis, 5 but paradoxically, they also mediate the regeneration of liver tissue after injury. 6 ,7 This study was designed to evaluate IL-18 in sera of infants and children suffering from acute hepatitis, chronic hepatitis and cirrhosis and to define its role as a predictive factor for chronicity of liver disease. Subjects and Methods: This cross-sectional study included 18 children suffering from acute viral hepatitis that lasted less than 60 days, 26 infants and children suffering from chronic hepatitis and 15 suffering from cirrhosis. They were attendants of the Hepatology Clinic of the New Children’s Hospital, Cairo University. Twenty-three, age and sex matched, clinically free infants were also included as a control group. Parents of the participating infants gave their consent to the trial. Inclusion criteria were based on pathology findings in the children suffering from a liver condition lasting more than 2 months. Children having acute viral ‘A’ hepatitis were included upon confirmation by detection of hepatitis A virus IgM in serum without percutaneous liver biopsy.