Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma

Abstract

Objectives:Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses.Whereas tetracyclineshave anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied.Methods: Peripheral blood mononuclear cells (PBMCs) from serum IgE+ allergic asthmatic subjects (n=11) and healthy controls (n=12) were infected with C. pneumoniae and cultured for 12 days with or without doxycycline (0.01-1.0 mg/L). IgE, interferon (IFN)-γ and interleukin (IL)-4 levels in supernatants were determined on days 1- 12post-infection,and C.pneumoniae DNA copynumbers in PBMC cultureweremeasuredonday2 (quantitative PCR).Results: C. pneumoniae-infected PBMCs from allergic asthmatic individuals had increased levels of IgE in supernatants compared with uninfected PBMCs (520% on day 10 post-infection, P=0.008). IgE levels in PBMC cultures from controls were undetectable (<0.3 ng/mL). Increases in C. pneumoniae-induced IgE in asthmatics correlated with those of C. pneumoniae-induced IL-4 (r=0.98; P<0.001), but not with IFN-γ. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (>70%, P=0.04) and IL-4 (75%, P=0.018), but not IFN-γ. The suppressive effect on IL-4 production remained significant even at concentrations of doxycycline that were subinhibitory (0.01 mg/L) for C. pneumoniae. In both asthmatic participants and controls, no significant effect of doxycycline on DNA copy numbers of C. pneumoniae was observed.Conclusions: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, inPBMCs fromIgE+allergicasthmaticsubjects.Thesefindings resultedfromtheimmunomodulatoryanti-allergicpropertiesof tetracyclines. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.