The Local Role of Tumor Necrosis Factor α in the Modulation of Neutrophil Function at Sites of Inflammation

John Yee, MD; Nicolas V. Christou, MD, PhD, FRCSC
Arch Surg. 1994;129(12):1249-1255. doi:10.1001/archsurg.1994.01420360039004.
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Objective:  To examine the hypothesis that tumor necrosis factor α (TNF-α) is an important local modulator of neutrophil function in the inflammatory microenvironment.

Design:  In vitro studies of host defense.

Patients:  A volunteer sample of healthy subjects.

Intervention:  Exudative neutrophils were collected from skin-blister chambers and functionally compared with blood neutrophils.

Methods:  Tumor necrosis factor α levels at sites of inflammation and neutrophil exudation were determined and compared with serum concentrations. Flow cytometry was used to evaluate neutrophil microbicidal activity and N-formyl-methionyl-leucyl-phenylalanine—induced changes in intracellular calcium and superoxide production. In vitro TNF-α was used to evaluate the nature and dose response of TNF-α–induced changes in neutrophil function.

Results:  Exudative neutrophils have an increased responsiveness to subsequent N-formyl-methionyl-leucyl-phenylalanine stimulation, as determined by changes in intracellular calcium. Microbicidal activity and superoxide production are also up-regulated compared with circulating neutrophils. The exudative microenvironment contains TNF-α at local levels that are capable of significantly enhancing neutrophil host defense.

Conclusions:  Tumor necrosis factor α may serve to enhance neutrophil function at sites of inflammation. Neutrophils become more cytotoxic and have an enhanced ability to respond to weak environmental signals.(Arch Surg. 1994;129:1249-1255)


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