Tumor necrosis factor alpha gene expression in human peritoneal macrophages is suppressed by extra-abdominal trauma
C. J. Hauser, S. Lagoo, A. Lagoo, E. Hale, K. J. Hardy, W. H. Barber, J. D. Bass and G. V. Poole
Department of Surgery, University of Mississippi Medical Center, Jackson, USA.
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 (PM phi) early after trauma.
DESIGN: Case-control study comparing cytokine messenger RNA (mRNA)
expression by PM phi from patients with extra-abdominal trauma with that of
both peripheral blood mononuclear cells (PBM) and PM phi 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, > or = 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 alpha (TNF-alpha), interleukin-1 beta,
IL-6, and IL-10 message by semiquantitative reverse-transcription
polymerase chain reaction. RESULTS: Normal PM phi expressed high levels of
TNF-alpha mRNA relative to PBM, but expression of the other proinflammatory
cytokines was equivalent to that of PBM. Peritoneal macrophage expression
of TNF-alpha mRNA was markedly (64-fold) decreased after trauma (P <
.001), when PBM expression of IL-10 mRNA was increased (P = .03).
CONCLUSIONS: Human PM phi constitutively show high levels of TNF-alpha
message expression, and this is down-regulated by polytrauma. This might
constitute a functionally "primed" state. If so, TNF-alpha down-regulation
might contribute to functional PM phi suppression after systemic injury.
