Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis.

OBJECTIVE AND DESIGN

To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis.

MATERIAL

Male BALB/c mice were used. Macrophages/Kupffer cells isolated from P. acnes-primed murine liver were used for the in vitro study.

TREATMENT

Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p. o.). Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice.

METHOD

Plasma TNFalpha estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study. The LPS-induced production of TNFalpha in vitro from the cultured macrophage/Kupffer cells was determined by ELISA.

RESULTS

Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them. Both agents attenuated the LPS-induced release of TNFalpha in vivo, and suppressed the TNFalpha production from the cultured macrophage/Kupffer cells.

CONCLUSIONS

These results suggest that rolipram and dbcAMP have potential to inhibit TNFalpha production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P. acnes/LPS hepatitis model.