Tumor necrosis factor alpha gene expression in human peritoneal macrophages is suppressed by extra-abdominal trauma.
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.


METHODS
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.


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


METHODS
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.


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


METHODS
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.
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D010537:Peritoneum / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha