Evaluation of the immunomodulatory effects of the macrolide antibiotic, clarithromycin, in female B6C3F1 mice: a 28-day oral gavage study.
The macrolide antibiotic, clarithromycin, is used extensively to treat bacterial infections associated with pneumonia, duodenal ulcers, and the advanced stages of human immunodeficiency viral (HIV) infection. In addition to its antimicrobial properties, several studies have indicated that clarithromycin also has anti-inflammatory and immunomodulatory properties. In this study, clarithromycin's immunomodulatory properties were evaluated using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate, and acquired cellular and humoral immune responses. Female B6C3F1 mice were treated daily by gavage with clarithromycin (0, 125, 250, and 500 mg/kg) for 28 days then evaluated for immunomodulation. Minimal immunological changes were observed after 28 days of treatment. A slight increase in the number of spleen antibody-forming cells was observed at the 250 mg/kg treatment level, but not at other doses. Serum IgM levels were unaffected by the clarithromycin treatment. A significant increase in the number of splenic macrophages was also observed in mice treated with 125 mg/kg of clarithromycin, but this increase was not observed at the other treatment levels. Innate and cell-mediated immunity, as measured by natural killer cell activity, and mixed leukocyte and cytotoxic T cell response, respectively, were unchanged following treatment with clarithromycin. These results suggest that the immune system is not a target for clarithromycin at doses of 500 mg/kg or below.
Karrow
N A
NA
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
McCay
J A
JA
Brown
R D
RD
Musgrove
D L
DL
Germolec
D R
DR
White
K L
KL
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000917:Antibody Formation / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D007075:Immunoglobulin M / Q000097:blood; D007441:Intubation, Gastrointestinal; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D018675:Toxicity Tests
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D007075:Immunoglobulin M; D017291:Clarithromycin