Lipopolysaccharide primes neutrophils for a rapid response to IL-10

Eur J Immunol. 2005 Jun;35(6):1877-85. doi: 10.1002/eji.200526088.


Responsiveness of human neutrophils to IL-10 was recently shown to be strictly dependent on the levels of IL-10R1 expression. Activation of signal transducer and activator of transcription 3 (STAT3) phosphorylation and induction of suppressor of cytokine signaling (SOCS)-3 protein by IL-10 are in fact negligible in circulating or freshly isolated ("time 0") neutrophils, but become readily measurable in neutrophils cultured for 4 h in the presence or absence of LPS. In this study, we show that modulation by IL-10 of LPS-induced TNF-alpha, CXCL8/IL-8 and IL-1 receptor antagonist (IL-1ra) mRNA accumulation in neutrophils already expressing a functional IL-10R and antigenic SOCS-3 (i.e. in "4-h-cultured" neutrophils) occurs with kinetics that are similar to those observed in "time 0" neutrophils, depends on de novo protein synthesis, but does not require SOCS-1, SOCS-3, heme oxygenase and Bcl-3 induction. By contrast, we show that IL-10 alone rapidly modulates the expression of TNF-alpha, CXCL8/IL-8 and IL-1ra mRNA, without any new protein synthesis requirement, if neutrophils have been previously exposed to LPS for at least 4 h. These findings suggest that LPS prepares neutrophils to optimally respond to IL-10 in terms of rapid gene modulation via mechanisms that, presumably, depend on specific LPS-induced protein(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Heme Oxygenase (Decyclizing) / physiology
  • Heme Oxygenase-1
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-10 / pharmacology*
  • Interleukin-8 / genetics
  • Lipopolysaccharides / pharmacology*
  • Membrane Proteins
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Protein Biosynthesis
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-10
  • Repressor Proteins / physiology
  • Sialoglycoproteins / genetics
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors / physiology
  • Tumor Necrosis Factor-alpha / genetics


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-8
  • Lipopolysaccharides
  • Membrane Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Repressor Proteins
  • SOCS3 protein, human
  • Sialoglycoproteins
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1