Toll-like receptor expression on peripheral blood mononuclear cells in asthmatics; implications for asthma management

J Clin Immunol. 2010 May;30(3):459-64. doi: 10.1007/s10875-009-9363-z. Epub 2010 Jan 14.

Abstract

Background: Accumulating evidence indicates that cells expressing Toll-like receptors (TLRs) play an important role in allergic diseases. The authors undertook this study to explore the hypothesis that TLR-mediated inflammatory signals are important from the perspective of asthma management.

Methods: The expressions of TLR1, TLR2, TLR3, TLR4, TLR6, and TLR9 and levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IFN-gamma) on the peripheral blood mononuclear cells (PBMCs) of 36 stable asthmatics on treatment (the on-treatment group), 15 asthmatics (the treatment-naïve group) before and after a 7-day course of oral prednisolone (30 mg/day), and on the PBMCs of 15 healthy controls were measured after in vitro stimulation using TLR-specific ligands.

Results: In the on-treatment group, TLR1, TLR2, TLR6, and TLR9 expressions on PBMCs were significantly different between asthmatics and controls. And the expression of TLR4 on PBMCs and TNF-alpha production stimulated by lipopolysaccharide (LPS), were significantly higher in mild to moderate than in severe asthmatics. Interestingly, in the treatment-naïve group, short-term prednisolone significantly increased LPS-induced TNF-alpha and IFN-gamma productions by PBMCs.

Conclusion: TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Asthma / pathology
  • Asthma / physiopathology
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Diglycerides / pharmacology
  • Disease Progression
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Lipopeptides / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Oligopeptides / pharmacology
  • Peptidoglycan / pharmacology
  • Prednisolone / administration & dosage*
  • Prednisolone / adverse effects
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*

Substances

  • Cytokines
  • Diglycerides
  • FSL-1 lipoprotein, synthetic
  • Inflammation Mediators
  • Lipopeptides
  • Lipopolysaccharides
  • Oligopeptides
  • Pam(3)CSK(4) peptide
  • Peptidoglycan
  • Toll-Like Receptors
  • Prednisolone