Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 138; no. 1; p. 165
• Main Authors: Wu, Jia-Feng, Wu, Tzee-Chung, Chen, Chien-Hung, Ni, Yen-Hsuan, Chen, Huey-Ling, Hsu, Hong-Yuan, Chang, Mei-Hwei
• Format: Journal Article
• Language: English
• Published: United States 01.01.2010
• Subjects: Adolescent; Adult; Cells, Cultured; Child; Female; Genotype; Hepatitis B e Antigens - blood; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - immunology; Humans; Infant; Interferon-gamma - genetics; Interleukin-10 - blood; Interleukin-10 - genetics; Interleukin-12 Subunit p40 - blood; Interleukin-12 Subunit p40 - genetics; Interleukin-2 - genetics; Interleukin-4 - genetics; Leukocytes - cytology; Leukocytes - metabolism; Male; Phenotype; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prospective Studies; Viral Load; Young Adult
• ISSN: 1528-0012
• DOI: 10.1053/j.gastro.2009.09.018

This prospective cohort study aimed to determine the effect of cytokines on spontaneous hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) infection. Polymorphisms in interleukin (IL)-2, IL-4, IL-10, IL-12beta, and interferon-gamma were evaluated in 288 HBeAg-positive chronic HBV patients (median initial age, 8.6 years; median follow-up duration, 19.3 years). Serum cytokine levels were determined in 154 subjects (53.5%) before and after HBeAg seroconversion by enzyme-linked immunosorbent assay analysis. Peripheral blood mononuclear cells (PBMC) were isolated from patients with chronic HBV infection and stimulated with HBV core antigen (HBcAg); data on cytokine genotypes and phenotypes were compared. The IL-10-1082 G/G and IL-12beta -10993C/G genotypes predicted early, spontaneous HBeAg seroconversion (hazard ratio [HRs] = 3.43 and 1.54; P < .001, and P < .004, respectively), based on multivariate survival analysis. The IL-10 -1082 G/G genotype was associated with higher serum levels of IL-10 and IL-12; the IL-12beta -10993 C/G genotype predicted higher levels of IL-12 secretion by PBMC after in vitro HBcAg stimulation (P = .04). Higher levels of serum IL-12 (>45 pg/mL) and IL-10 (>70 pg/mL) were associated with early, spontaneous HBeAg seroconversion (HR = 1.52 and 1.48; P = .04 and .02, respectively). The IL-10-1082 G/G is associated with higher serum IL-10 and IL-12 levels and IL-12beta -10993 C/G is associated with increased secretion of IL-12 in response to HBcAg stimulation of PBMC. Both genotypes are associated with early, spontaneous HBeAg seroconversion. Higher serum levels of IL-10 and IL-12 in HBeAg-positive patients are correlated with early, spontaneous HBeAg seroconversion.