Role of IL-8, IL-10, IL-12, IFN- γ and TNF- α in the Immunopathogenesis of Acute Hepatitis B Virus Infection

Abstract

AIM: To study the role of IL-8, IL-10, IL-12, IFN-γ AND TNF-α in immunopathogenesis of HBV infection. METHODS: Eight hundred and forty consecutive patients with hepatitis were screened by serological markers for acute HBV (AHB) and were genotyped using modified Kirschberg’s method. Patients were graded clinically and biochemically. Serum IL-8, IL-10, IL-12, IFN-γ and TNF-α levels were estimated in them and in healthy controls by enzyme immunoassay. RESULTS: Seventy six cases of AHB with genotype D were identified and cytokines estimated. IFN-γ, IL-12, TNF-α, IL-8 levels were significantly higher than in the healthy controls at 27.26±7.39 pg/mL (p<0.001), 54.6 pg/mL (p<0.05), 176.32 pg/mL (p<0.001), 202.32 pg/mL (p<0.0001) respectively. In NNI cases, median IFN-γ, IL-12 and TNF- α levels were higher at 52.351 pg/mL, 57.12 pg/mL and 240 pg/mL p<0.001 respectively. In contrast IL-8 and IL-10 were lower in NNI. All five cytokines appeared to play a role in seroconversion to anti HBs. IFN-γ and IL-12 levels were highest in patients negative for HBV DNA, their median levels being 89.218 pg/mL and 67.23 pg/mL, respectively. HBeAg was independently associated with elevated levels of IL-8 and low levels of IL-12. Severe cases of liver disease, ESLD were significantly associated with elevated levels of TNF-α (190 pg/mL) and IL-8 (208 pg/mL) and depressed levels of IFN-γ (14.32 pg/mL), IL-12 (32.13 pg/mL) and IL-10 (16.52 pg/mL). CONCLUSION: Both IFN-γ and IL-12 appear to play a dominant role in AHB and in causing HBV DNA and HBeAg negativity. Elevated levels were associated with best clinical status. IL-8 and TNF- α was associated with presence of both HBV DNA and HBeAg pointing to its non-protective role. Low levels of IL-10 were an important finding in this study pointing to the patients inability to overcome the viral invasion. These results demonstrate that noncytopathic antiviral mechanisms may contribute to viral clearance during acute HBV infection.