Clarithromycin potentiates glucocorticoid responsiveness in patients with asthma: results of a pilot study.
BACKGROUND
Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects.


OBJECTIVE
To determine whether clarithromycin, by virtue of its anti-inflammatory effects, enhances glucocorticoid sensitivity.


METHODS
Open-label, pilot study in a paired design (pre- and posttreatment).


METHODS
Seven patients, mean age 27 (range 15 to 42 years), with mild to moderate asthma under good control.


METHODS
Clarithromycin (500 mg) was administered twice daily for 10 days with blood drawn for lymphocyte stimulation assays at baseline, and again upon completion of therapy. Lymphocytes were stimulated with phytohemagglutinin in the presence and absence of increasing concentrations of clarithromycin and dexamethasone (DEX).


RESULTS
At baseline, clarithromycin alone did not cause a significant degree of suppression of T-lymphocyte activation, yet clarithromycin significantly enhanced the sensitivity of lymphocytes to suppression by DEX as measured by a shift in the DEX dose-response curve by at least 6-fold (P = 0.04). In addition, a 10-day course of clarithromycin resulted in: 1) a significant decrease in the inhibitory concentration which results in a 50% reduction in proliferation for DEX alone, thereby increasing glucocorticoid sensitivity (P = 0.04); 2) heightened inhibitory effect of clarithromycin alone (P = 0.03); and 3) a sustained suppressive effect with the combination of clarithromycin and DEX on the inhibition of lymphocyte stimulation (P = 0.01).


CONCLUSIONS
Clarithromycin acts synergistically with DEX in suppressing lymphocyte activation. In addition, a 10-day course resulted in a significant treatment effect as evidenced by lower inhibitory concentration which results in a 50% reduction in proliferation value for DEX, a heightened response to clarithromycin alone, and a consistent degree of suppression of lymphocyte stimulation when clarithromycin and DEX were used together.
Spahn
J D
JD
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. spahnj@njc.org
Fost
D A
DA
Covar
R
R
Martin
R J
RJ
Brown
E E
EE
Szefler
S J
SJ
Leung
D Y
DY
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010865:Pilot Projects; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D017291:Clarithromycin