PMID- 23749949 OWN - NLM STAT- MEDLINE DCOM- 20140310 LR - 20220317 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 68 IP - 10 DP - 2013 Oct TI - Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma. PG - 2363-8 LID - 10.1093/jac/dkt179 [doi] AB - OBJECTIVES: 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. 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 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (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-gamma. 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-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. 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 immunomodulatory anti-allergic properties of tetracyclines. FAU - Dzhindzhikhashvili, M S AU - Dzhindzhikhashvili MS AD - Center for Allergy and Asthma Research at SUNY Downstate, State University of New York (SUNY) Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203, USA. FAU - Joks, Rauno AU - Joks R FAU - Smith-Norowitz, Tamar AU - Smith-Norowitz T FAU - Durkin, Helen G AU - Durkin HG FAU - Chotikanatis, Kobkul AU - Chotikanatis K FAU - Estrella, Eva AU - Estrella E FAU - Hammerschlag, Margaret R AU - Hammerschlag MR FAU - Kohlhoff, Stephan A AU - Kohlhoff SA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130607 PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Anti-Bacterial Agents) RN - 0 (IL4 protein, human) RN - 0 (Immunologic Factors) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - N12000U13O (Doxycycline) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Anti-Bacterial Agents/*administration & dosage MH - Asthma/*drug therapy/immunology MH - Bacterial Load MH - Cells, Cultured MH - Chlamydophila Infections/*complications/microbiology MH - Chlamydophila pneumoniae/immunology MH - Doxycycline/*administration & dosage MH - Female MH - Humans MH - Immunoglobulin E/*blood MH - Immunologic Factors/*administration & dosage MH - Interleukin-4/*metabolism MH - Leukocytes, Mononuclear/immunology/microbiology MH - Male MH - Middle Aged MH - Young Adult OTO - NOTNLM OT - cytokines OT - immunomodulation OT - inflammation OT - tetracyclines EDAT- 2013/06/12 06:00 MHDA- 2014/03/13 06:00 CRDT- 2013/06/11 06:00 PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2014/03/13 06:00 [medline] AID - dkt179 [pii] AID - 10.1093/jac/dkt179 [doi] PST - ppublish SO - J Antimicrob Chemother. 2013 Oct;68(10):2363-8. doi: 10.1093/jac/dkt179. Epub 2013 Jun 7.