DEFECTIVE INTERLEUKIN-2 PRODUCTION IN CHILDREN WITH CHRONIC HEPATITIS-B - ROLE OF ADHERENT CELLS

Background: Chronic hepatitis B (CHB) virus infection Is associated wi th functional abnormalities of cell-mediated immunity, defective inter ferons alpha and gamma synthesis, and interleukin-2 receptor expressio n. In this study, interleukin-2 (IL-2) production and the role of adhe rent cells was evaluated in 25 children chronically infected with hepa titis B virus. Methods: IL-2 activity was measured by bioassay in supe rnatants of phytohemoagglutinin-stimulaled peripheral blood mononuclea r cells. In a few patients, IL-2 concentration was also immunochemical ly determined. Coculture experiments using a mixture of adherent cells and lymphocytes from healthy children and patients with CHB were also performed. Results: Children with CHB showed lower IL-2 production th an healthy controls. In patients, IL-2 activity was 34.7 +/- 22.5 U/ml as compared to 152.6 +/- 78.5 U/ml of controls. Immunochemical quanti tation of IL-2 confirmed a lower IL-2 production in patients, No corre lation was found between the functional T-cell defect and the severity of liver damage, degree of viral replication, and duration of the dis ease. In co-culture experiments, adherent cells from HBsAg-positive pa tients inhibited IL-2 production following mitogen stimulation of cont rol non-adherent cells by 67%. The inhibitory effect, mediated by pati ents' adherent cells, was abolished by blocking with indomethacin pros taglandins, that are potent local immunomodulators released by adheren t cells. Conclusions: Our results further support the observation that in children with CHB virus infection, adherent cells play an importan t role in the inappropriate regulation of immune response, an effect b eing likely mediated by prostaglandins. (C) 1997 Lippincott-Raven Publ ishers.