Inhibition of angiogenesis as a new therapeutic target in the treatment of lepromatous leprosy

摘要

Background: Angiogenesis was suggested to have a significant role in the pathogenesis of leprosy. However, the benefit of inhibiting angiogenesis in lepromatous leprosy patients has not previously been studied. The purpose of this study was to evaluate angiogenesis in leprosy patients before and after treatment with multidrug therapy (MDT) with and without minocycline.Methods: A total of 40 patients with lepromatous leprosy were enrolled in this study. They were categorized into two equal groups (A and B), each formed of 20 patients. Group A received World Health Organization MDT, and Group B received MDT combined with minocycline, which has a known antiangiogenic effect. Microvascular density (MVD) in dermal granuloma was evaluated in both groups by immunostaining with CD31 and CD34 markers before and after 6 months of treatment.Results: With CD31 immunostaining, the mean MVD in Group A significantly decreased from 39.1 ± 3.1 vessels (v)/high power field (HPF) to 16.5 ± 2.7 v/HPF, and in Group B it significantly decreased from 38.3 ± 2.5 v/HPF to 7.6 ± 1.9 v/HPF. CD34 immunostaining also showed a significant decrease of MVD from 42.2 ± 3.1 v/HPF to 18.8 ± 2.4 v/HPF in Group A, and in Group B it significantly decreased from 43.7 ± 2.3 v/HPF to 11.5 ± 1.6 v/HPF. The reduction of MVD was significantly higher in Group B compared with in Group A (P?< 0.0001). Moreover, there was a significant reduction in bacterial density (assessed by bacterial index) in the cutaneous lesions of in Group B (decreased from 4.9 ± 0.3 to 1.4 ± 0.2) compared with in Group A (decreased from 5.1 ± 0.4 to 2.3 ± 0.4).Conclusion: The synergistic effect of MDT and minocycline seems to be promising in the treatment of lepromatous leprosy. It significantly reduces angiogenesis and rapidly eliminates lepra bacilli from the skin that enables a rapid control and elimination of the disease.