INCREASED PROSTAGLANDIN I-2 AND THROMBOXANE A(2) PRODUCTION BY RAT DENTAL-PULP AFTER INTRAVENOUS ADMINISTRATION OF ENDOTOXIN

The effect of systemic endotoxin (lipopolysaccharide from Escherichia coli 0111:B4) on prostaglandin I-2 (PGI(2)) and thromboxane A(2) (TXA( 2)) production by rat dental pulp was investigated. Intravenous inject ion of endotoxin increased ex vivo production of both PGI(2) and TXA(2 ) by the pulp tissue, when determined by radioimmunossay. A significan t effect on PGI(2) and TXA(2) production was observed with endotoxin d oses of greater than 2 and 0.4 mg/kg, respectively. A significant incr ease was also observed at 30 min after injection of 10 mg/kg endotoxin , reaching a maximum after 60 min for both PG and TX production. Endot oxin (10 mg/kg for 60 min) also increased TXA(2) but not PGI(2) produc tion in lung tissue, but had no effect in jejunal tissue. Indomethacin (10 mu M) completely inhibited PGI(2) and TXA(2) production by the pu lp of physiological saline- and endotoxin-treated rats. Further, arach idonic acids (10 mu M) significantly increased PG and TX production by the pulp of saline- but not of endotoxin-treated rats. Endotoxin (100 mu g/ml) had no in vitro effect on PG or TX production when incubated with isolated pulp, lung and jejunal tissues, suggesting that the end otoxin-induced increases in PG and TX production are an indirect effec t. The endotoxin-induced increase in TXA(2) production, but not in PGI (2) production, by the pulp tissue was significantly suppressed by WEB 2170, a platelet-activating factor (PAF) antagonist. These results in dicate that arachidonate metabolism in pulp tissue is susceptible to e ndotoxaemia in comparison with the lung and jejunum, and further sugge st that the endotoxin-induced increase in, at least, TXA(2) production by the pulp is mediated by PAF.