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The Role of Fracture-Associated Soft Tissue Injury in the Induction of Systemic Inflammation and Remote Organ Dysfunction After Bilateral Femur Fracture

Kobbe, Philipp MD*; Vodovotz, Yoram MD†‡; Kaczorowski, David J MD; Billiar, Timothy R MD; Pape, Hans-Christoph MD*

Journal of Orthopaedic Trauma: July 2008 - Volume 22 - Issue 6 - p 385-390
doi: 10.1097/BOT.0b013e318175dd88
Original Article

Objectives: The storage of preformed cytokines in soft tissue as well as the immunocompetence of adipocytes has been reported. We hypothesized that fracture-associated soft tissue injury plays a pivotal role in the induction of systemic inflammation and remote organ dysfunction after fracture.

Materials and Methods: Male C57/BL6 mice sustained either severe soft tissue injury to both thighs (STI), bilateral femur fracture with minimal soft tissue injury (Fx), or the combination of both (Fx+STI) and were euthanized 6 hours after injury. Serum cytokine concentrations were measured using the Luminex multiplexing platform, and serum ALT levels were measured with the Vitros 950 Chemistry System. Hepatic myeloperoxidase activity, a marker for polymorphonuclear cell infiltration, and hepatic IL-6 levels were determined using ELISA kits. Hepatic permeability changes were assessed via measurement of edema formation.

Results: STI as well as Fx both induced significantly elevated serum IL-6 and L-10 levels as compared with Sham animals (P < 0.05). Further, serum IL-6 and IL-10 levels were significantly higher after STI as compared with Fx (P < 0.05). Serum KC and MCP-1 levels were significantly elevated after STI but not after Fx (P < 0.05). STI as well as Fx resulted in significantly increased serum ALT levels and hepatic polymorphonuclear cell infiltration. The combination of both injuries resulted in further increased systemic inflammatory mediators as well as marked liver inflammation and dysfunction represented by significantly elevated serum ALT levels, hepatic polymorphonuclear cell infiltration, hepatic IL-6 concentrations, and hepatic edema formation as compared with Sham animals (P < 0.05).

Conclusions: Although STI and Fx both induced a systemic inflammatory response, this was more pronounced after STI. However, the combination of both injuries (Fx+STI) was required to induce marked liver dysfunction. Our data indicate that fracture-associated soft tissue injury is a major contributor to the systemic inflammatory response after bilateral femur fracture. This should be recognized especially in multiply injured patients, who are susceptible to systemic inflammation with remote organ dysfunction.

From the *Department of Orthopedic Surgery; †Department of Surgery; and ‡Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh.

Accepted for publication March 20, 2008.

This work was supported by National Institutes of Health Trauma Center Grant P50-GM053789.

The authors state that they have no financial interest in the products mentioned within this article.

Reprints: Philipp Kobbe, MD, Department of Orthopaedic Surgery, University of Pittsburgh, Kaufmann Medical Building, Suite 1010,3471 Fifth Avenue, Pittsburgh, PA 15213 (e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.