Role of tumor necrosis factor-alpha in disease states and inflammation
Strieter, R.M.; Kunkel, S.L.; Bone, R.C.
Critical Care Medicine 21(10 Suppl): S447-S463
1993
ISSN/ISBN: 0090-3493 PMID: 8403983 Document Number: 411473
Objective: To review the animal and human data defining the role of tumor necrosis factor (TNF) in the pathogenesis of the septic shock syndrome, and systemic inflammatory response syndrome, and related pathologic states. Data Sources: The international English language literature from 1975 to present formed the basis for this review. MEDLINE was used to identify pertinent animal and human studies. Study Selection: Those animal and human studies that focused on the mechanisms of action of TNF, its role in the inflammatory cytokine network, and the potential use of anti-TNF therapies were emphasized. Data Extraction: Animal studies were selected based on the relevance of the model to the pathogenesis of the human systemic inflammatory response syndrome. When they provided supportive evidence, human studies were selected on the basis of study design. Data Synthesis: TNF plays a major role in systemic inflammatory response syndrome secondary to infection, burns, trauma or hemorrhagic shock, and pancreatitis. TNF influences the outcome of other infectious processes, including allograft rejection, ischemia-reperfusion injury, delayed-typed hypersensitivity, and granuloma development. The administration of related fusion proteins may limit organ damage and decrease mortality rate. Conclusions: Although the regulated release of TNF may exert normal physiologic effects, the uncontrolled production of TNF may lead to organ dysfunction and death. TNF mediates a variety of other physiologic processes that are unrelated to sepsis syndrome. New anti-TNF therapies appear to attenuate the injurious actions of TNF.