Hepatic cytoprotection by prostaglandins: Theories unlimited

16,16 Dimethyl prostaglandin E 2 (dmPGE 2 ), a known cytoprotective agent, was examined for its ability to alter the course of fulminant hepatitis in an experimental model of fulminant viral hepatitis, murine hepatitis virus type 3 (MHV‐3). Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD 50 ) of MHV‐3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 ± 619 IU/liter). In contrast, animals treated with dmPGE 2 either before or after infection (up to 48 h) demonstrated a marked reduction in both histologic and biochemical evidence of liver damage as characterized by normal blood glucose, total CO 2 , and ALT determinations (mean ALT, 63 ± 40 IU/liter). Treatment of infected mice with PGF 2 demonstrated no cytoprotective effects. High titers of infectious virus were recovered from the livers of both dmPGE 2 ‐treated and ‐untreated animals throughout the course of infection. In a parallel in vitro study, dmPGE 2 (10 −4 –10 −8 M) demonstrated a similar cytoprotective effect on monolayers of isolated cultured hepatocytes from fully susceptible BALB/cJ mice infected at a multiplicity of infection of 0.1, 1.0, and 10.0. In addition, splenic macrophages recovered from infected and untreated BALB/cJ mice demonstrated a marked augmentation in procoagulant activity (PCA) from a basal 10 ± 5 mU/10 6 splenic macrophages to a maximum of 615 ± 102 mU/10 6 splenic macrophages, whereas no increase in macrophage PCA was detected in infected animals treated with dmPGE 2 . These results suggest that dmPGE 2 , without detectably altering viral replication or infectivity in vivo , confers a marked cytoprotective effect on hepatocytes both in vivo and in vitro , and prevents the induction of macrophage PCA in vivo in fully susceptible BALB/cJ mice after murine hepatitis virus type 3 infection.