Effect of minocycline and doxycycline on IgE responses.
BACKGROUND
We have recently found that the tetracycline minocycline suppresses inflammatory responses in serum immunoglobulin (Ig)E-positive asthmatic patients, and that IgE levels can decrease in these patients. The mechanism by which minocycline suppresses these responses is unknown.


OBJECTIVE
We have now investigated the ability of the tetracyclines, minocycline and doxycycline, to regulate IgE responses of peripheral blood mononuclear cells (PBMC) obtained from serum IgE-positive asthmatic patients.


METHODS
The distributions of CD3+, CD4+, CD8+, and CD19+ lymphocytes in peripheral blood of serum IgE-positive asthmatic patients and IgE-negative nonasthmatic controls, and cytokine-specific mRNA expression by their PBMC were determined by flow cytometry (reverse transcriptase-polymerase chain reaction). Serum Ig levels also were determined (nephelometry, fluoroenzymeimmunoassay, enzyme-linked immunoadsorbent assay; n = 7/group). PBMC (1.5 x 10(6)/mL) were cultured with anti-CD40 monoclonal antibody and recombinant human interleukin-4 in the presence/absence of minocycline or doxycycline (0.1 to 10 microg/mL), and IgE levels in supernatants determined on days 0, 3, and 10 (enzyme-linked immunoadsorbent assay).


RESULTS
Asthmatic and nonasthmatic subjects had similar numbers of blood CD4+ T cells (779/mm3 +/- 73 and 766 +/- 115, respectively) and CD19+ B-cells (239/mm3 +/- 35 and 379 +/- 95, respectively); however, CD8+ T cell numbers were decreased in asthmatic compared with nonasthmatic subjects (378/mm3 +/- 66 and 568 +/- 53, respectively; P = 0.045). High IgE levels were detected in supernatants of asthmatic PBMC on day 10 (28 ng/mL +/- 12), whereas control IgE levels did not change (<2.5 ng/mL). When either minocycline or doxycycline was included in culture, IgE production by asthmatic PBMC was strongly suppressed in dose-dependent fashion on day 10 (>80% with 10 microg/mL); control IgE did not change (<2.5 ng/mL).


CONCLUSIONS
The results are consistent with the idea that the therapeutic benefits obtained by asthmatic patients from minocycline may, in part, result from IgE suppression.
Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA. tsmith-norowitz@downstate.edu
Tamar A
TA
Smith-Norowitz
Martin H
MH
Bluth
Hazel
H
Drew
Kevin B
KB
Norowitz
Seto
S
Chice
Vipin N
VN
Shah
Maja
M
Nowakowski
Alan S
AS
Josephson
Helen G
HG
Durkin
Rauno
R
Joks
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000145:classification; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
D018927:Anti-Asthmatic Agents; D016207:Cytokines; D012333:RNA, Messenger; D007073:Immunoglobulin E; D008911:Minocycline; D004318:Doxycycline