TY - JOUR
T1 - Prostaglandin E2 inhibits in vitro and in vivo lymphocyte responses in allogeneic transplantation
AU - Stonc, Christopher D.
AU - Rosengard, Bruce R.
AU - Boorstein, Stephen M.
AU - Robbins, Robert C.
AU - Hennein, Hani A.
AU - Clark, Richard E.
N1 - Funding Information:
Surgery Branch, National Heart, Lung, and Blood Institute, and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Prostaglandin E, (PGE,) has been shown to have 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 PGE, 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 E, (DMPGE,), a stable analogue of PGE,, significantly prolonged the survival of heterotopic cardiac allografts from ACI to LBN rats: 10.4 f 1.7 days versus 5.7 f 1.1 days (mean 2 standard error of the mean) (p 5 0.001). In 1 animal, DMPGE, apparently led to the induction of long-term tolerance. Mixed lymphocyte cultures using splenocytes from naive LBN and ACI rostaglandins are now well-recognized modulators of P local immune function [1,2]. The E series prostaglandins have been shown by numerous investigators [3-51 to play a role in the suppression of immune responses after burn or trauma injury. This suppression has been attributed to the inhibition of both interleukin-2 (IL-2) production and IL-2-dependent lymphocyte proliferation [6]. Other IL-2 modulators are currently in wide use for immunosuppression after transplantation. However, prostaglandins, particularly prostaglandin E, (PGE,), have not been thoroughly studied as transplant immunosuppressants. 16,16-dimethyl prostaglandin E, (DMPGE,) is a long acting, injectable analogue of PGE,. In this study we tested the hypothesis that exogenous administration of PGE, as DMPGE, would suppress alloreactivity both in vivo and in vitro and, therefore, prolong solid-organ allograft survival.
PY - 1990/6
Y1 - 1990/6
N2 - Prostaglandin E, (PGE2) has been shown to have 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 <- 0.001). In 1 animal, DMPGE2 apparently ied 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-dependend suppression of the mixed lymphocyte response with concentrations as low as 1 × 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.
AB - Prostaglandin E, (PGE2) has been shown to have 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 <- 0.001). In 1 animal, DMPGE2 apparently ied 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-dependend suppression of the mixed lymphocyte response with concentrations as low as 1 × 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.
UR - https://www.scopus.com/pages/publications/0025437597
UR - https://www.scopus.com/pages/publications/0025437597#tab=citedBy
U2 - 10.1016/0003-4975(90)90868-7
DO - 10.1016/0003-4975(90)90868-7
M3 - Article
C2 - 2142409
AN - SCOPUS:0025437597
SN - 0003-4975
VL - 49
SP - 927
EP - 931
JO - The Annals of Thoracic Surgery
JF - The Annals of Thoracic Surgery
IS - 6
ER -