Differences in LPS and PepG Induced Release of Inflammatory Cytokines in Orthopedic Trauma

Abstract

Trauma is associated with immune paresis which may predispose to postoperative sepsis. We characterized the ex vivo cytokine responses to bacterial cell wall components in whole blood from 8 patients undergoing a major musculoskeletal trauma in the form of total hip replacement. Preoperatively, at the end of operation, and at days 1 and 6 postoperatively, patient blood was obtained, anticoagulated, and incubated at 37°C in the presence of peptidoglycan (PepG) or lipopolysaccharide (LPS). Plasma cytokines were measured by enzyme immunoassay. The numbers of leucocytes, monocytes, and neutrophils were unchanged at the end of surgery, while there were significant increases at postoperative days 1 and 6. We observed significant reductions in tumor necrosis factor–α (TNF-α) and interleukin 10 (IL-10) responses to PepG at the end of surgery, which was disproportional to the nonsignificant reductions in circulating monocytes, suggesting a functional suppression. However, at postoperative day 1 the responses were recovered. There were no significant changes in responses of TNF-α to LPS stimulation at the end of surgery, while there were significant depressions at postoperative days 1 and 6. The expression of IL-10 was significantly depressed at the end of surgery and at day 6. There were modest changes in PepG- and LPS-induced expression of interleukin 8 (IL-8) during the experiments. On the basis of these observations, we conclude that a musculoskeletal trauma is associated with reduced expression of TNF-α and IL-10 by whole blood leucocytes when exposed to endotoxin, but there is a difference between gram-positive endotoxin (PepG) and gram-negative endotoxin (LPS).

KEYWORDS:

• immune response
• inflammatory cytokines
• interleukin 8
• interleukin 10
• orthopaedic surgery
• trauma
• tumor necrosis factor–α