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

作者：Dzhindzhikhashvili M S; Joks Rauno; Smith Norowitz Tamar; Durkin Helen G; Chotikanatis Kobkul; Estrella Eva; Hammerschlag Margaret R; Kohlhoff Stephan A^*

来源：Journal of Antimicrobial Chemotherapy, 2013, 68(10): 2363-2368.

DOI：10.1093/jac/dkt179

• tetracyclines
• inflammation
• immunomodulation
• cytokines

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. %26lt;br%26gt;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)-gamma and interleukin (IL)-4 levels in supernatants were determined on days 1-12post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR). %26lt;br%26gt;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 (%26lt;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%26lt;0.001), but not with IFN-gamma. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (%26gt;70%, P = 0.04) and IL-4 (75%, P = 0.018), but not IFN-gamma. 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. %26lt;br%26gt;Conclusions: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-gamma, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatoryanti-allergic properties of tetracyclines.

• 出版日期2013-10