2941083

pubmed:Citation

1

Prostaglandins are said to influence T and B cell function by inhibiting the generation of interleukin 2 (IL 2) and the formation of suppressor lymphocytes. After bone marrow transplantation, patients usually have a profound immunodeficiency that persists in recipients with chronic graft-v-host disease (GVHD) and generally resolves in long-term survivors without GVHD. In vitro tests of lymphocyte function such as allogeneic mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) have been shown to be impaired in many patients. We postulated that prostaglandin E2 (PGE2) plays a role in the impaired in vitro tests. To test this hypothesis, we studied in vitro tests in the presence of PGE2 antagonists, indomethacin, and anti-PGE2 antiserum with cells from 22 short-term patients (less than 100 days postgrafting) and 32 long-term survivors with or without GVHD. Results show that blockade of PGE2 release by indomethacin and anti-PGE2 significantly (P less than .01) enhanced the MLC (+67%) and the CML responses (+10.5%) of cells from long-term survivors with chronic GVHD but not from those of long-term, stable recipients. No enhancement of MLC and CML activity was observed with cells from donors of long-term recipients. In patients shortly after marrow grafting, enhancement in the MLC was not significant. However, CML activity in this patient group was significantly increased (+12.5% in recipients with no GVHD, 8.5% in those with acute GVHD, P less than .01). Indomethacin also suppressed the activity of nonspecific suppressor cells in patients with chronic GVHD. When cells from patients with chronic GVHD were treated with recombinant IL 2 and IL 2 combined with indomethacin, it was possible to get an additional augmentation of lymphocyte proliferation after the addition of indomethacin to IL 2-treated cultures. Thus it is very likely that PGE2 inhibits T lymphocyte proliferation, not exclusively by inhibition of IL2 production or activity. We conclude that PGE2, among other factors, may play a role in the pathogenesis of the immunodeficiency after transplantation. PGE2 does not act primarily by interfering with IL2 but presumably by inducing a suppressorlike activity.

eng

AIM

MEDLINE

0006-4971

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102-7

pubmed-meshheading:2941083-Adolescent, pubmed-meshheading:2941083-Adult, pubmed-meshheading:2941083-Bone Marrow Transplantation, pubmed-meshheading:2941083-Child, pubmed-meshheading:2941083-Child, Preschool, pubmed-meshheading:2941083-Dinoprostone, pubmed-meshheading:2941083-Female, pubmed-meshheading:2941083-Graft vs Host Disease, pubmed-meshheading:2941083-Humans, pubmed-meshheading:2941083-Immune Sera, pubmed-meshheading:2941083-Indomethacin, pubmed-meshheading:2941083-Interleukin-2, pubmed-meshheading:2941083-Lymphocyte Activation, pubmed-meshheading:2941083-Lymphocyte Culture Test, Mixed, pubmed-meshheading:2941083-Male, pubmed-meshheading:2941083-Middle Aged, pubmed-meshheading:2941083-Prostaglandins E, pubmed-meshheading:2941083-T-Lymphocytes, Regulatory, pubmed-meshheading:2941083-Transplantation, Homologous

Inhibition of prostaglandin E2 restores defective lymphocyte proliferation and cell-mediated lympholysis in recipients after allogeneic marrow grafting.