November 1995

Tumor Necrosis Factor α Gene Expression in Human Peritoneal Macrophages Is Suppressed by Extra-abdominal Trauma

Author Affiliations

From the Department of Surgery (Drs Hauser, S. Lagoo, Barber, and Poole and Ms Hale), the Division of Rheumatology and Molecular Immunology, Department of Medicine (Dr Hardy), the Department of Pathology (Dr A. Lagoo), and the Division of Biostatistics, Department of Preventive Medicine (Dr Bass), The University of Mississippi Medical Center, Jackson, and Jackson Veterans Affairs Medical Center.

Arch Surg. 1995;130(11):1186-1192. doi:10.1001/archsurg.1995.01430110044008

Background:  Trauma is believed to activate immunocytes but paradoxically also increases the risk of intraperitoneal infection.

Objective:  To investigate these events by evaluating changes in the cytokine control networks of human peritoneal macrophages (PMø) early after trauma.

Design:  Case-control study comparing cytokine messenger RNA (mRNA) expression by PMø from patients with extra-abdominal trauma with that of both peripheral blood mononuclear cells (PBM) and PMø obtained from healthy individuals.

Setting:  Level I trauma center and basic science laboratory in a university hospital center.

Patients:  Six patients with polytrauma (Injury Severity Score, ≥15) with clinically negative diagnostic peritoneal lavages performed on routine indications at admission to the emergency department and six healthy age- and sex-matched individuals undergoing inguinal herniorrhaphy under local anesthesia.

Interventions:  Peritoneal macrophages were isolated from diagnostic peritoneal lavages in trauma patients. Identical lavages were performed through the hernia sac in the control group.

Measurements:  Cellular RNA was assayed for tumor necrosis factor α (TNF-α), interleukin-1β, IL-6, and IL-10 message by semiquantitative reverse-transcription polymerase chain reaction.

Results:  Normal PMø expressed high levels of TNF-α mRNA relative to PBM, but expression of the other proinflammatory cytokines was equivalent to that of PBM. Peritoneal macrophage expression of TNF-α mRNA was markedly (64-fold) decreased after trauma (P<.001), when PBM expression of IL-10 mRNA was increased (P=.03).

Conclusions:  Human PMø constitutively show high levels of TNF-α message expression, and this is down-regulated by polytrauma. This might constitute a functionally "primed" state. If so, TNF-α down-regulation might contribute to functional PMø suppression after systemic injury.(Arch Surg. 1995;130:1186-1192)