Differential effects of three antibiotics on T helper cell cytokine expression.
OBJECTIVE
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.
Williams
Auriol C
AC
Academic Unit of Anaesthesia & Intensive Care, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Galley
Helen F
HF
Watt
Alison M
AM
Webster
Nigel R
NR
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D016207:Cytokines; D024841:Fluoroquinolones; D011804:Quinolines; D015847:Interleukin-4; D015759:Ionomycin; D002939:Ciprofloxacin; D007371:Interferon-gamma; D017291:Clarithromycin; D013755:Tetradecanoylphorbol Acetate; D000077266:Moxifloxacin