title: Tetracycline-mediated IgE isotype-specific suppression of ongoing human and murine IgE responses in vivo and murine memory IgE responses induced in vitro.
abstract: We previously reported that minocycline treatment of allergic asthmatic patients had oral steroid sparing effects and improved their clinical status and that minocycline suppressed in vitro induction of IgE responses by their PBMC. The effect of minocycline on human or animal IgE responses in vivo has not been studied. Allergic asthmatics (serum IgE: 505 +/- 535 IU ml(-1)) were given minocycline (150 mg po to 250 mg po BID) as add-on therapy to standard care for up to 10 months; control subjects (IgE: 405 +/- 472 IU ml(-1)) received standard care (n = 6 per group). Serum immunoglobulin (IgM, IgG, IgE and IgA) levels were determined monthly (Nephelometry, Unicap Total IgE Fluoroenzyme immunoassay). BALB/c mice (n = 6 per group) were injected intraperitoneally with benzylpenicilloyl(14)-Keyhole limpet hemocyanin (BPO(14)-KLH) in alum on days 0, 21 and 42, fed with minocycline or doxycycline (10-100 mg kg(-1)) on day 44 and numbers of BPO-specific IgG(1), IgE and IgA antibody-forming cell (AFC) in mesenteric LN and spleen and serum immunoglobulin levels were determined on days 46-70 (enzyme-linked immunosorbent spot assay, ELISA). The ability of minocycline or doxycycline to suppress in vitro induction of murine memory IgE responses also was investigated. Minocycline strongly suppressed serum IgE levels of allergic asthmatics (9% per month) (P = 0.012). Minocycline (and doxycycline) also strongly suppressed peak murine IgE AFC and serum IgE responses (>95, approximately 75%, respectively) and in vitro induction of memory IgE responses by murine mesenteric LN and spleen cells (>95%). Tetracycline suppression of all human and murine IgE responses was IgE isotype specific. Suppression of murine IgE responses in vivo was dose dependent and lasted 5-7 days.
authors.affiliation: Department of Medicine, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. rauno.joks@downstate.edu
authors.forename: Rauno
authors.initials: R
authors.lastname: Joks
authors.forename: Tamar
authors.initials: T
authors.lastname: Smith-Norowitz
authors.forename: Maja
authors.initials: M
authors.lastname: Nowakowski
authors.forename: Martin H
authors.initials: MH
authors.lastname: Bluth
authors.forename: Helen G
authors.initials: HG
authors.lastname: Durkin
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D004318:Doxycycline / Q000627:therapeutic use; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D010400:Penicillin G / Q000009:adverse effects; D013154:Spleen / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018926:Anti-Allergic Agents; D007073:Immunoglobulin E; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D008911:Minocycline; D004318:Doxycycline; D010400:Penicillin G