Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis.
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.
Ertel
W
W
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Morrison
M H
MH
Ayala
A
A
Chaudry
I H
IH
D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D007111:Immunity, Cellular / Q000187:drug effects; D007239:Infections / Q000150:complications / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000276:immunology* / Q000628:therapy
D007376:Interleukin-2; D008222:Lymphokines; D002738:Chloroquine; D015232:Dinoprostone