Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis
W. Ertel, M. H. Morrison, A. Ayala and I. H. Chaudry
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Hemorrhagic shock causes a severe suppression of cellular immunity and an
increased susceptibility to sepsis that may be due to increased release of
prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion
of prostaglandin E2 by macrophages in vitro, the effects of chloroquine
administration in vivo following hemorrhagic shock on macrophage
prostaglandin E2 secretion and on depressed cellular immunity were
examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean
blood pressure of 35 mm Hg, which was maintained for 60 minutes, and
adequately, resuscitated. Mice then received intramuscular injections of
either saline (vehicle) or chloroquine (10 mg/kg of body weight).
Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin
A-dependent splenocyte proliferation, and interleukin 2 in splenocyte
supernatants (CTLL 20 interleukin 2-dependent proliferation) were
determined 2 or 24 hours later. Hemorrhage caused a significant decrease of
splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours,
while prostaglandin E2 secretion from macrophages was elevated at 2 hours.
Chloroquine treatment attenuated depression of splenocyte functions and
reduced prostaglandin E2 release. Furthermore, chloroquine treatment
decreased the mortality of septic mice after hemorrhage to levels
comparable with those of sham-operated mice. Thus, chloroquine may be a
useful adjunct in the clinical setting for the treatment of shock-induced
immunodepression and increased susceptibility to sepsis following
hemorrhage.
