title: Lipopolysaccharide and tumor necrosis factor-alpha synergy potentiate serum-dependent responses of rat macrophages.
abstract: 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.
authors.affiliation: Department of Pediatrics, St. Louis University Medical School, Missouri 63110, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Fox
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: T F
authors.initials: TF
authors.lastname: Tracy
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha