Fluid Resuscitation Attenuates Early Cytokine mRNA Expression after Peritonitis

Abstract

Objective To study the hypothesis that fluid resuscitation alters cytokine gene expression after experimental murine peritonitis. Materials and Methods Mice underwent cecal ligation and puncture (CLP) to induce peritonitis and were randomized to receive variable amounts of normal saline (0, 0.25, 1.0 mL subcutaneously) and serum (0 or 0.1 mL) after operation. Hepatic and small intestinal (ileal) tissue were harvested at 3 or 6 hours after CLP, and total tissue RNA was extracted. Reverse transcriptase polymerase chain reaction was used to provide relative quantitation of tumor necrosis factor-alpha and interleukin (IL)-1beta messenger RNA (mRNA) compared with beta-actin. Results CLP without resuscitation resulted in significant increases in hepatic tumor necrosis factor-alpha mRNA (1190% at 6 hours compared with normal animals), and IL-1beta mRNA (1475%), and intestinal 1L-1beta mRNA (1243%). Volume administration attenuated cytokine expression at both 3 and 6 hours, and saline seemed to have more potent effects than serum. The volume of resuscitation correlated with survival at 18 hours. Survival in the saline (1 mL) + serum group was 90% at 18 hours compared with 20 to 40% in the groups with little or no resuscitation. Overall, there were no survivors at 30 hours. Conclusions Fluid resuscitation (amount, composition, timing) should be an important consideration in the utilization of experimental infection models. Furthermore, optimization of the patient's intravascular volume status during sepsis may have important effects on immune responses, in addition to improving hemodynamic variables.