Selective inhibition of TNF-alpha or IL-1 beta does not affect E. coli-induced inflammation in human whole blood

Mol Immunol. 2010 May;47(9):1774-82. doi: 10.1016/j.molimm.2010.02.026. Epub 2010 Mar 23.


Inhibition of the inappropriate and excessive inflammatory response has been a main issue in sepsis-related research. Historically, TNF-alpha and IL-1 beta have been postulated as key mediators in sepsis, but selective inhibition of these cytokines has failed in clinical trials. Recently it was found that inhibition of upstream recognition by complement and CD14 could efficiently reduce Escherichia coli (E. coli)-induced inflammation. An ex vivo model with lepirudin-anticoagulated human whole blood was used to explore the significance of selective inhibition of TNF-alpha and IL-1 beta in E. coli-induced inflammation. The effect of TNF-alpha, IL-1 beta, complement and CD14 on the inflammatory response was assessed by adding highly specific neutralizing agents to these mediators. Proinflammatory cytokines, expression of CD11b and oxidative burst were measured. The controls included relevant isotype-matched immunoglobulins and peptides. Selective inhibition of TNF-alpha or IL-1 beta had no impact on E. coli-induced release of proinflammatory cytokines, CD11b-upregulation or oxidative burst. In contrast, the combined inhibition of complement and CD14 virtually abolished these responses. These data suggest that both TNF-alpha and IL-1 beta are downstream mediators and as single mediators play a limited role within the complex inflammatory reactions induced by E. coli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • CD11b Antigen / blood
  • Cytokines / blood
  • Escherichia coli / immunology*
  • Etanercept
  • Humans
  • Immunoglobulin G / pharmacology
  • Inflammation / blood
  • Inflammation / immunology*
  • Inflammation / prevention & control
  • Inflammation Mediators / blood
  • Infliximab
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology*
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Respiratory Burst / immunology
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • CD11b Antigen
  • Cytokines
  • Immunoglobulin G
  • Inflammation Mediators
  • Interleukin-1beta
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept