Gram-positive and Gram-negative bacteria elicit different patterns of pro-inflammatory cytokines in human monocytes

Cytokine. 2005 Jun 21;30(6):311-8. doi: 10.1016/j.cyto.2004.05.008. Epub 2005 Apr 7.


Pro-inflammatory cytokines secreted by tissue macrophages recruit polymorphonuclear leukocytes and evoke fever, cachexia and production of acute phase proteins. This study investigates whether Gram-positive and Gram-negative bacteria equally and efficiently trigger production of the pro-inflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF-alpha in human monocytes. A range of aerobic and anaerobic Gram-positive and Gram-negative bacteria were killed by UV-light and added in different concentrations to human monocytes. Cytokines were measured in 24 h supernatants by ELISA. Gram-positive and Gram-negative bacteria were equally efficient inducers of IL-1 beta, but Gram-positive bacteria generated twice as much TNF-alpha as did Gram-negative bacteria (p<0.001 for 25 and 250 bacteria/cell). In contrast, Gram-negative bacteria induced at least twice as much IL-6 and IL-8 as did Gram-positive bacteria (p<0.001 for 2.5, 25 and 250 bacteria/cell). While the cytokine responses to LPS were similar to those induced by the corresponding amount of Gram-negative bacteria, the strong IL-1 beta and TNF-alpha responses to Gram-positive bacteria could not be induced by soluble peptidoglycan or lipotheicoic acid. The particular nature of the bacteria, thus seem to modify the response to Gram-positive bacterial components. The different cytokine profiles evoked by Gram-positive and Gram-negative bacteria might optimize clearance of bacteria that differ in cell wall structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall / metabolism
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / metabolism
  • Gram-Negative Bacteria / metabolism*
  • Gram-Positive Bacteria / metabolism*
  • Humans
  • Inflammation
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Kinetics
  • Monocytes / metabolism*
  • Monocytes / microbiology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays


  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha