Topic: The Antibiotics Doxycycline and Minocycline Inhibit the Inflammatory Responses
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The Journal of Infectious Diseases 2009;199:000-000 � 2009 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2009/19909-00XX$15.00 DOI: 10.1086/597807
MAJOR ARTICLE
Andrea L. F. Bernardino,
Deepak Kaushal, and
Mario T. Philipp
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana
Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP‐1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-α, interleukin (IL)-6, and IL‐8 in a dose‐dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete‐stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down‐regulated. Functionally, phosphorylation of IκBα and binding of NF‐κB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.
Received 14 August 2008; accepted 17 November 2008; electronically published 17 March 2009. Reprints or correspondence: Dr. Mario T. Philipp, Div. of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, 18703 Three Rivers Rd., Covington, LA 70433 ([email protected]).
Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants NS048952 and RR00164); Centers for Disease Control and Prevention (grant UO1‐CI000153).
NOTE. Notice who "owns" this data? Interesting, wouldn't you say?
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