Open AccessLIPOPOLYSACCHARIDE AND TUMOR NECROSIS FACTOR-± SYNERGY POTENTIATE SERUM-DEPENDENT RESPONSES OF RAT MACROPHAGES
Author(s) -
Eben S. Fox,
Lei Wang,
Thomas F. Tracy
Publication year - 1996
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/00024382-199606000-00007
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , cd14 , macrophage , polymyxin b , cytokine , chemistry , sepsis , immunology , receptor , biology , in vitro , biochemistry , antibiotics
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are major mediators of sepsis and multiple organ failure. Serum-mediated macrophage activation requires lipopolysaccharide (LPS) and its serum binding protein, lipopolysaccharide binding protein as a ligand for the receptor CD14. This study was designed to determine whether cytokines participate in regulation of serum-mediated LPS activation. Rat macrophages were stimulated with LPS with and-without TNF-alpha or IL-1 beta and activation was determined by detection of TNF-alpha by specific enzyme-linked immunosorbent assay or TNF-alpha mRNA by Northern blot analysis. The addition of TNF-alpha but not IL-1 beta, in the presence of serum, leads to potentiation of macrophage activation after LPS stimulation. This effect could be specifically inhibited by neutralization of LPS with polymyxin B or an antibody against TNF-alpha. This study shows that LPS and TNF-alpha synergize to potentiate serum-mediated macrophage activation. These results demonstrate another element of the control mechanism of cytokine secretion following macrophage activation in sepsis.