Increased monocyte TNF-alpha message stability contributes to trauma patients' increased TNF production
Department of Medicine, Division of Gastroenterology
Adult; Aged; Aged, 80 and over; Animals; Biological Assay; Burns; Female; Humans; Inflammation; Male; Mice; Middle Aged; Monocytes; RNA, Messenger; Reference Values; Regression Analysis; *Transcription, Genetic; Tumor Necrosis Factor-alpha; Wounds and Injuries
Life Sciences | Medicine and Health Sciences
Post-trauma elevation of tumor necrosis factor alpha (TNF-alpha) appears to be critical in mediating many symptoms of systemic inflammatory response syndrome (SIRS), resulting in late mortality. Although increased monocyte (mphi) TNF-alpha production plays a pivotal role in this TNF-alpha elevation, the molecular mechanisms leading to increased mphi TNF-alpha production have yet to be elucidated. We demonstrate that, although TNF-alpha mRNA levels are increased in all trauma patients' mphi, which produce elevated levels of TNF-alpha protein, in the majority of patients, these increased TNF-alpha mRNA levels are under normal transcriptional and posttranscriptional control. Consequently, the increased TNF-alpha production by these patients' mphi is probably due to preactivation of these mphi by trauma-released mediators. However, a small minority of patients, whose mortality rate was 57%, produce TNF-alpha of primarily the membrane-associated type. The mphi TNF-alpha mRNA accumulation of these patients in response to in vitro stimulation is significantly augmented. All of these patients experienced SIRS. In this subset of patients' mphi, TNF-alpha mRNA stability was aberrantly increased. Such an increase in TNF-alpha mRNA stability could lead to devastatingly prolonged production of TNF-alpha protein. This demonstration of increased TNF-alpha mRNA stability in post-trauma mphi represents a novel correlation of elevated membrane-associated TNF-alpha protein, increased mortality, and a mechanism for this occurrence.
J Leukoc Biol. 1997 Oct;62(4):524-34.
Journal of leukocyte biology
Furse, Robert K.; Kodys, Karen; Zhu, Dan; and Miller-Graziano, Carol L., "Increased monocyte TNF-alpha message stability contributes to trauma patients' increased TNF production" (1997). Open Access Articles. 1143.