EFFECTS OF D-MYO-INOSITOL-1,2,6-TRISPHOSPHATE ON EICOSANOID FORMATIONIN BURNED SKIN

D-myo-Inositol-1,2,6-trisphosphate (IP3) has been shown to reduce edem a and progressive ischemia following experimental skin burns, The mech anism(s) are not identified but could be related to antiinflammatory e ffects of the agent, In the present ex vivo study we compared the effe cts of IP3 with those of saline and indomethacin on eicosanoid formati on by normal and burned rat skin, In burned skin IP3 treatment reduced the release of thromboxane B-2 (TXB(2)) (P < 0.01) and leukotriene B- 4 (LTB(4)) (P < 0.05) but there was only a weak trend for less prostag landin E (PGE) compared to burned control animals receiving saline. In domethacin reduced the release of TXB(2) (P < 0.01), and PGE (P < 0.00 1), but not LTB(4) from burned skin compared to skin from saline-treat ed burned animals. In nonburned skin IP3 increased the release of PGE (P < 0.01) and LTB(4) (P < 0.01), but did not significantly influence TXB(2) accumulation in the incubation fluid compared to the saline-tre ated group, Indomethacin reduced the release of TXB(2) (P < 0.001) and PGE (P < 0.001), but increased LTB(4) (P < 0.001) in normal skin comp ared to the saline-treated group. In conclusion, IP3 inhibited the rel ease of TXB(2) and LTB(4) from burned skin ex vivo, but increased PGE and LTB(4) release from normal skin. These results suggest that the mo de of action of IP3 differs from that of nonsteroidal antiinflammatory drugs, The effects of IP3 on the arachidonic acid cascade also seem t o differ in burned versus normal skin. (C) 1996 Academic Press, Inc.