Differential effects of three antibiotics on T helper cell cytokine expression.

Auriol Williams, Helen Frances Galley, Nigel Robert Webster

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Objectives: To test whether ciprofloxacin, moxifloxacin and clarithromycin affect the expression of the T helper (Th) cell cytokines, interferon-gamma and interleukin-4. Quinolone and macrolide antibiotics are routinely used for the treatment of critically ill patients with sepsis. These antibiotics modulate some aspects of immune cell function. Alteration in the profile of Th cell cytokine expression will affect the T helper cell ratio and subsequent immune responses.

Methods: Following ethics committee approval and informed consent, mononuclear cells were isolated from 20 healthy volunteers using single density gradient centrifugation. Cells were incubated with ciprofloxacin (0-100 mg/L), moxifloxacin (0-50 mg/L) or clarithromycin (0-125 mg/L) and stimulated with phorbol myristate acetate and ionomycin. For flow cytometric analysis, cells were stained with antibodies to CD3 and CD4, prior to permeabilization with saponin and intracellular staining with anti-interleukin-4 and anti-interferon-gamma.

Results: Both moxifloxacin and ciprofloxacin dose-dependently decreased interferon-gamma and interleukin-4 expression by Th cells (both P < 0.0001). Only interleukin-4 expression however, was affected by clarithromycin (P = 0.04). There was no change in the Th1/Th2 ratio for moxifloxacin or ciprofloxacin, but the Th1/Th2 ratio increased with increasing concentrations of clarithromycin, from a median [range] of 5.3 [1.3-16.0] without antibiotic to 9.1 [1.8-18.8] at 125 mg/L (P = 0.017).

Conclusions: Moxifloxacin and ciprofloxacin had pronounced effects on both Th1 and Th2 cytokine expression, without altering Th1/Th2 ratios. However, clarithromycin decreased only interleukin-4 expression such that the Th1/Th2 ratio increased. Since a Th1 profile is considered favourable for resolution of infection, elucidation of immunomodulatory profiles of antibiotics may permit more rational antibiotic choice in future.

Original languageEnglish
Pages (from-to)502-506
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume56
Issue number3
DOIs
Publication statusPublished - 2005

Keywords

  • lymphocytes
  • interferon-gamma
  • interleukin-4
  • quinolones
  • clarithromycin
  • immunomodulation
  • macrolides
  • T cells
  • transcription factors
  • human neutrophils
  • gene-expression
  • epithelial-cells
  • human monocytes
  • KAPPA-B
  • interluekin-8
  • moxifloxacin

Cite this

Differential effects of three antibiotics on T helper cell cytokine expression. / Williams, Auriol; Galley, Helen Frances; Webster, Nigel Robert.

In: Journal of Antimicrobial Chemotherapy, Vol. 56, No. 3, 2005, p. 502-506.

Research output: Contribution to journalArticle

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AU - Webster, Nigel Robert

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N2 - Objectives: To test whether ciprofloxacin, moxifloxacin and clarithromycin affect the expression of the T helper (Th) cell cytokines, interferon-gamma and interleukin-4. Quinolone and macrolide antibiotics are routinely used for the treatment of critically ill patients with sepsis. These antibiotics modulate some aspects of immune cell function. Alteration in the profile of Th cell cytokine expression will affect the T helper cell ratio and subsequent immune responses.Methods: Following ethics committee approval and informed consent, mononuclear cells were isolated from 20 healthy volunteers using single density gradient centrifugation. Cells were incubated with ciprofloxacin (0-100 mg/L), moxifloxacin (0-50 mg/L) or clarithromycin (0-125 mg/L) and stimulated with phorbol myristate acetate and ionomycin. For flow cytometric analysis, cells were stained with antibodies to CD3 and CD4, prior to permeabilization with saponin and intracellular staining with anti-interleukin-4 and anti-interferon-gamma.Results: Both moxifloxacin and ciprofloxacin dose-dependently decreased interferon-gamma and interleukin-4 expression by Th cells (both P < 0.0001). Only interleukin-4 expression however, was affected by clarithromycin (P = 0.04). There was no change in the Th1/Th2 ratio for moxifloxacin or ciprofloxacin, but the Th1/Th2 ratio increased with increasing concentrations of clarithromycin, from a median [range] of 5.3 [1.3-16.0] without antibiotic to 9.1 [1.8-18.8] at 125 mg/L (P = 0.017).Conclusions: Moxifloxacin and ciprofloxacin had pronounced effects on both Th1 and Th2 cytokine expression, without altering Th1/Th2 ratios. However, clarithromycin decreased only interleukin-4 expression such that the Th1/Th2 ratio increased. Since a Th1 profile is considered favourable for resolution of infection, elucidation of immunomodulatory profiles of antibiotics may permit more rational antibiotic choice in future.

AB - Objectives: To test whether ciprofloxacin, moxifloxacin and clarithromycin affect the expression of the T helper (Th) cell cytokines, interferon-gamma and interleukin-4. Quinolone and macrolide antibiotics are routinely used for the treatment of critically ill patients with sepsis. These antibiotics modulate some aspects of immune cell function. Alteration in the profile of Th cell cytokine expression will affect the T helper cell ratio and subsequent immune responses.Methods: Following ethics committee approval and informed consent, mononuclear cells were isolated from 20 healthy volunteers using single density gradient centrifugation. Cells were incubated with ciprofloxacin (0-100 mg/L), moxifloxacin (0-50 mg/L) or clarithromycin (0-125 mg/L) and stimulated with phorbol myristate acetate and ionomycin. For flow cytometric analysis, cells were stained with antibodies to CD3 and CD4, prior to permeabilization with saponin and intracellular staining with anti-interleukin-4 and anti-interferon-gamma.Results: Both moxifloxacin and ciprofloxacin dose-dependently decreased interferon-gamma and interleukin-4 expression by Th cells (both P < 0.0001). Only interleukin-4 expression however, was affected by clarithromycin (P = 0.04). There was no change in the Th1/Th2 ratio for moxifloxacin or ciprofloxacin, but the Th1/Th2 ratio increased with increasing concentrations of clarithromycin, from a median [range] of 5.3 [1.3-16.0] without antibiotic to 9.1 [1.8-18.8] at 125 mg/L (P = 0.017).Conclusions: Moxifloxacin and ciprofloxacin had pronounced effects on both Th1 and Th2 cytokine expression, without altering Th1/Th2 ratios. However, clarithromycin decreased only interleukin-4 expression such that the Th1/Th2 ratio increased. Since a Th1 profile is considered favourable for resolution of infection, elucidation of immunomodulatory profiles of antibiotics may permit more rational antibiotic choice in future.

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KW - interleukin-4

KW - quinolones

KW - clarithromycin

KW - immunomodulation

KW - macrolides

KW - T cells

KW - transcription factors

KW - human neutrophils

KW - gene-expression

KW - epithelial-cells

KW - human monocytes

KW - KAPPA-B

KW - interluekin-8

KW - moxifloxacin

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DO - 10.1093/jac/dki251

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VL - 56

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EP - 506

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

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