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. DESIGN: Open-label, pilot study in a paired design (pre- and posttreatment). PARTICIPANTS: 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.
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. DESIGN: Open-label, pilot study in a paired design (pre- and posttreatment). PARTICIPANTS: 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.
Authors: Francesca Gay; S Vincent Rajkumar; Morton Coleman; Shaji Kumar; Tomer Mark; Angela Dispenzieri; Roger Pearse; Morie A Gertz; John Leonard; Martha Q Lacy; Selina Chen-Kiang; Vivek Roy; David S Jayabalan; John A Lust; Thomas E Witzig; Rafael Fonseca; Robert A Kyle; Philip R Greipp; A Keith Stewart; Ruben Niesvizky Journal: Am J Hematol Date: 2010-09 Impact factor: 10.047
Authors: P Zarogoulidis; N Papanas; I Kioumis; E Chatzaki; E Maltezos; K Zarogoulidis Journal: Eur J Clin Pharmacol Date: 2011-11-22 Impact factor: 2.953
Authors: Mark H Gotfried; Rose Jung; Chad R Messick; Israel Rubinstein; Kevin W Garey; Keith A Rodvold; Larry H Danziger Journal: Curr Ther Res Clin Exp Date: 2004-01
Authors: Bruce J Kirenga; Jeremy I Schwartz; Corina de Jong; Thys van der Molen; Martin Okot-Nwang Journal: Afr Health Sci Date: 2015-12 Impact factor: 0.927
Authors: Se Jin Park; Jin Ho Kook; Ha Kyun Kim; Sung Hoon Kang; Sae Hee Lim; Hyun Jin Kim; Kyung Won Kim; Tae Hoon Kim; Sang Hag Lee Journal: Br J Pharmacol Date: 2015-10-17 Impact factor: 8.739