Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis.
OBJECTIVE
To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis.


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


METHODS
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.


METHODS
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.
Taguchi
I
I
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., Osaka, Japan. taguchi@tanabe.co.jp
Oka
K
K
Kitamura
K
K
Sugiura
M
M
Oku
A
A
Matsumoto
M
M
D000818:Animals; D003994:Bucladesine / Q000627:therapeutic use*; D006520:Hepatitis, Animal / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011425:Propionibacterium acnes / Q000472:pathogenicity*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D020889:Rolipram; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D020889:Rolipram