A sequential study of hepatic structural damage following the intravenous injection of Corynebacterium parvum

Sequential histological and fine structural changes were studied in liver from 4.5 min to 21 days after a single intravenous injection of Corynebacterium parvum in the rat. A previously unreported effect of the micro-organism, the formation of eosinophilic inclusion bodies within hepatocytes, was observed between 15 min and 24 h of injection. These structures were most common in periportal hepatocytes at 2 h. The structural, enzyme- and immunohistochemical features of these bodies suggest that they represent a consequence of sub-lethal cell injury, affecting the endoplasmic reticulum or Golgi apparatus; resolution occurred within 24 h. The ingestion of C. parvum by phagocytes and the deposition of fibrin within sinusoids preceded the development of acute and chronic parenchymal and portal tract inflammation, leading to self-limiting granulomatous hepatitis. Lethal cell injury was represented by the presence of single-cell and confluent hepatocyte necrosis. Intravenous C. parvum causes sublethal and lethal hepatocyte damage, seen as the formation of cytoplasmic bodies and hepatocyte necrosis, respectively. Disseminated intravascular coagulation may mediate these changes via local hypoxia. This model could prove useful in the study of granulomatous hepatitis and in the evaluation of anti-inflammatory agents.