Induction of T helper cell type 1 response and elimination of HBeAg during treatment with IL-12 in a patient with therapy-refractory chronic hepatitis B.
This study reports the increase of immunoregulatory T helper cell type 1 response and elimination of HBV-DNA during IL-12 therapy in a patient with chronic hepatitis B virus infection who had not responded to three previous interferon-alpha therapies and one treatment with Famciclovir over a period of 6 years. The patient received IL-12 at a dose of 0.5 microgram/kg bodyweight weekly. Peripheral blood mononuclear cells were isolated before and during IL-12 application and incubated for 7 days with specific type 1 (purified protein derivative) and type 2 (tetanus-toxoid) TH cell antigens as well as with a macrophage/monocyte activating antigen (Bacille Calmette-Guérin). In the supernatants cytokines were determined by a double-sandwich ELISA. After 8 weeks HBV-DNA became negative and HBeAg seroconversion to anti-HBeAg occurred. Immunologically the loss of viremia was accompanied by a strong increase of the purified protein derivative-induced production of the type 1 cytokine interferon-gamma (1219 pg/mL before, 13,138 pg/mL after IL-12 therapy). Furthermore, Bacille Calmette-Guérin-induced secretion of the macrophage/monocyte-associated cytokines IL-1, tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor was higher at the end of therapy. This case indicates that IL-12 enhances type 1 T helper cell activity which may be a predisposition for elimination of HBeAg and successful treatment of hepatitis B.
Barth
H
H
Medizinische Klinik, Innere Medizin II, Tübingen, Germany. reinhild.klein@med.uni-tuebingen.de
Klein
R
R
Berg
P A
PA
Wiedenmann
B
B
Hopf
U
U
Berg
T
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D018664:Interleukin-12 / Q000627:therapeutic use*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D017211:Treatment Failure
D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D018664:Interleukin-12; D000410:Alanine Transaminase