Premium
Murine concanavalin A–induced hepatitis is prevented by interleukin 12 (IL‐12) antibody and exacerbated by exogenous IL‐12 through an interferon‐γ–dependent mechanism
Author(s) -
Nicoletti Ferdinando,
Di Marco Roberto,
Zaccone Paola,
Salvaggio Antonio,
Magro Gaetano,
Bendtzen Klaus,
Meroni PierLuigi
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.17701
Subject(s) - concanavalin a , hepatitis , immunology , cytokine , interleukin , monoclonal antibody , interferon gamma , interferon , antibody , medicine , tumor necrosis factor alpha , biology , in vitro , biochemistry
Concanavalin A (ConA)‐induced hepatitis is a cell‐mediated immunoinflammatory condition similar to human autoimmune hepatitis. We investigated the role of interleukin 12 (IL‐12) in hepatitis induced in NMRI and C57/BL6 mice by a single injection of ConA. Recombinant murine IL‐12 administered 24 hours and 1 hour prior to ConA exacerbated both transaminase activities in plasma and histologic signs of hepatitis. These markers of liver injury were significantly reduced by prophylactic, but not therapeutic treatment with anti–IL‐12 monoclonal antibody (mAb). The disease‐modulatory effects of IL‐12 and anti–IL‐12 mAb were associated with profound and reverse modifications of a ConA‐induced increase in the circulating levels of IL‐4, IL‐6, interferon gamma (IFN‐γ) and tumor necrosis factor (TNF). Relative to control animals receiving ConA alone, the plasma levels of these cytokines were all augmented in IL‐12/ConA‐treated mice and diminished in anti–IL‐12 mAb/ConA‐treated mice. Anti–IFN‐γ mAb also impeded the appearance of IL‐12/ConA‐induced hepatitis. Thus, IL‐12–induced production of IFN‐γ might play a role in mediating the hepatitis‐inducing effect of ConA. However, IL‐12p40–deficient C57/BL6 mice were as susceptible as wild‐type controls to the hepatitis‐inducing effect of ConA.