Prostaglandin E2 inhibits in vitro and in vivo lymphocyte responses in allogeneic transplantation.
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.
Stone
C D
CD
Surgery Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Rosengard
B R
BR
Boorstein
S M
SM
Robbins
R C
RC
Hennein
H A
HA
Clark
R E
RE
D015064:16,16-Dimethylprostaglandin E2 / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D007166:Immunosuppressive Agents; D011459:Prostaglandins E, Synthetic; D015064:16,16-Dimethylprostaglandin E2