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

• Published in: Journal of antimicrobial chemotherapy 2013-10, Vol.68 (10), p.2363-2368
• Main Authors: Dzhindzhikhashvili, M S, Joks, Rauno, Smith-Norowitz, Tamar, Durkin, Helen G, Chotikanatis, Kobkul, Estrella, Eva, Hammerschlag, Margaret R, Kohlhoff, Stephan A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Antibiotics; Asthma; Asthma - drug therapy; Asthma - immunology; Bacterial Load; Cell culture; Cells, Cultured; Chlamydophila Infections - complications; Chlamydophila Infections - microbiology; Chlamydophila pneumoniae; Chlamydophila pneumoniae - immunology; Doxycycline - administration & dosage; Female; Gram-negative bacteria; Humans; Immunoglobulin E - blood; Immunoglobulins; Immunologic Factors - administration & dosage; Interferon; Interleukin-4 - secretion; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - microbiology; Male; Middle Aged; Patients; Young Adult
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkt179

Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses. Whereas tetracyclines have anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied. 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 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR). 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 (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. Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.