IL-10 IS INVOLVED IN THE PROTECTIVE EFFECT OF DIBUTYRYL CYCLIC ADENOSINE-MONOPHOSPHATE ON ENDOTOXIN-INDUCED INFLAMMATORY LIVER-INJURY

The effects of exogenous cAMP, dibutyryl cAMP (DBcAMP) on LPS-induced liver injury were examined in mice made hypersensitive to LPS by treat ment with i.v, injection of Propionibacterium acnes, In vivo administr ation of DBcAMP significantly protected P. acnes-treated mice from LPS -induced liver injury, including apoptosis of hepatocytes. DBcAMP sign ificantly increased circulating IL-10 level in correlation with suppre ssion of the TNF-alpha level after LPS challenge in P, acnes-treated m ice, Treatment with anti-IL-10 mAb abrogated the protective effect of DBcAMP on LPS-induced liver injury, Similar to in vivo findings, addit ion of DBcAMP to in vitro culture of liver adherent cells from P. acne s-treated mice enhanced IL-10 synthesis after LPS stimulation, These r esults suggest that the increment in IL-10 production by liver adheren t cells is involved in the protective effect of DBcAMP on LPS-induced inflammatory liver injury.