title: 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: OBJECTIVE
  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)-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).
  
  
  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, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.
authors.affiliation: 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.
authors.forename: M S
authors.initials: MS
authors.lastname: Dzhindzhikhashvili
authors.forename: Rauno
authors.initials: R
authors.lastname: Joks
authors.forename: Tamar
authors.initials: T
authors.lastname: Smith-Norowitz
authors.forename: Helen G
authors.initials: HG
authors.lastname: Durkin
authors.forename: Kobkul
authors.initials: K
authors.lastname: Chotikanatis
authors.forename: Eva
authors.initials: E
authors.lastname: Estrella
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hammerschlag
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Kohlhoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D058491:Bacterial Load; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000150:complications* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology; D004318:Doxycycline / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007155:Immunologic Factors / Q000008:administration & dosage*; D015847:Interleukin-4 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; C508598:IL4 protein, human; D007155:Immunologic Factors; D015847:Interleukin-4; D007073:Immunoglobulin E; D004318:Doxycycline
keywords: cytokines; immunomodulation; inflammation; tetracyclines