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Inhibition of prostaglandin E2 restores defective lymphocyte proliferation
and cell-mediated lympholysis in recipients after allogeneic marrow
grafting
HG Klingemann, MS Tsoi and R Storb
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.
Volume 68,
Issue 1,
pp. 102-107,
07/01/1986
Copyright © 1986 by The American Society of Hematology
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