Effect of naloxone on immune responses after hemorrhagic shock

Objective: To determine whether naloxone administration after hemorrhagic s hock has any beneficial or deleterious effect on immune responses. Background Data: Hemorrhagic shock is known to produce immunodepression in both humans and experimental animals. Although studies suggest that endogen ous opioids play a role in immune regulation in adverse circulatory conditi ons, it remains controversial whether these opioids exert beneficial or det rimental effects on immunity after shock. Moreover, little information is a vailable concerning the effects of opioid receptor blockade using naloxone on cell-mediated immunity and endocrine responses after shock. Methods: Male C3H/HeN mice (25 g) were bled to and maintained at a mean art erial blood pressure of 35 +/- 5 mm Hg for 1 hr, The shed blood was then re turned along with lactated Ringer's solution (two times the shed blood volu me) to provide fluid resuscitation, The animals were randomized to receive either naloxone (1 mg/kg iv) or an equal volume of vehicle (saline) after t he shed blood was returned, i.e., immediately before crystalloid resuscitat ion, and were killed at 2 hrs after resuscitation to obtain splenocytes, ma crophages (peritoneal and splenic), and blood. Measurements and Main Results: Bioassays revealed significantly decreased r elease of all studied interleukins (interleukins-1, -2, -3, and -6) by peri toneal and splenic macrophages as well as significantly decreased splenocyt e proliferative capacity after shock in vehicle-treated mice, Naloxone admi nistration after hemorrhage resulted in either similar or even more decreas ed levels of interleukin release compared with vehicle-treated hemorrhaged mice. Significantly increased plasma corticosterone concentrations were obs erved in vehicle-treated animals compared with control animals. Naloxone ad ministration did not have any significant effects on corticosterone plasma concentrations after hemorrhage. Conclusions: These findings indicate the importance of the endogenous opioi d system for the maintenance of immunity in adverse circulatory conditions, i.e., hemorrhage. Although additional studies involving different doses an d/or times of naloxone administration may provide different results, the pr esent findings raise the concern that naloxone administration in the trauma tized host may have deleterious effects because it decreases peritoneal mac rophage and splenic immune functions.