Prostaglandin E2 (PGE2) has been shown to a clear role in the suppression of immune responses after burn and trauma injury. This probably results from inhibition of interleukin-2 production. This study examined the effects of PGE2 in vivo on the survival of solid-organ allografts and in vitro on the rat allogeneic mixed lymphocyte response. Administration of 16,16-dimethyl prostaglandin E2 (DMPGE2), a stable analogue of PGE2, significantly prolonged the survival of heterotopic cardiac allografts from ACI to LBN rats: 10.4 +/- 1.7 days versus 5.7 +/- 1.1 days (mean +/- standard error of the mean) (p less than or equal to 0.001). In 1 animal, DMPGE2 apparently led to the induction of long-term tolerance. Mixed lymphocyte cultures using splenocytes from naive LBN and ACI rats to which DMPGE2 was added showed a dose-dependent suppression of the mixed lymphocyte response with concentrations as low as 1 x 10(-7) mol/L. Splenocytes harvested from treated animals with functioning but histologically rejecting hearts demonstrated a marked decrease in mixed lymphocyte response to donor (ACI) stimulators compared with naive LBN controls (3,804 +/- 603 versus 27,395 +/- 2,668 cpm, n = 4), but maintained a normal response to third-party (Wistar Furth) stimulators. We conclude that DMPGE2 suppressed solid-organ allograft rejection, inhibited the allogeneic mixed lymphocyte response, and induced donor-specific in vitro hyporesponsiveness.
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