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Wolfgang Ertel, MD; Mary H. Morrison, MS; Alfred Ayala, PhD; Irshad H. Chaudry, PhD

Arch Surg. 1992;127(1):70-76.

Abstract
• 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.

(Arch Surg. 1992;127:70-76)

Author Affiliations
From the Shock and Trauma Research Laboratories (Drs Ertel, Ayala, and Chaudry and Ms Morrison), and the Departments of Surgery (Drs Ertel, Ayala, and Chaudry and Ms Morrison), Microbiology (Dr Ayala), and Physiology (Dr Chaudry), Michigan State University, East Lansing, Mich. Dr Ertel is now with the Chirurgische Klinik und Poliklinik der Ludwig-Maximilians-Universitaet, Muenchen, Klinikum Grosshadern, Munich, Germany.

Footnotes
Accepted for publication September 8, 1991.

Read before the 11th Annual Meeting of the Surgical Infection Society, Fort Lauderdale, Fla, April 9, 1991.

Reprint requests to the Department of Surgery, Michigan State University, B424 Clinical Center, East Lansing, Ml 48824-1315 (Dr Chaudry)

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