The involvement of endothelial mediators in leprosy

Abstract

Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

Fig. 1. : VCAM-1 in leprosy. (A) Comparison of VCAM-1 serum levels in non-reactional leprosy patients (NR) vs healthy controls (HC) (p = 0.0009); (B) immunohistochemical findings of VCAM-1 in skin lesions of NR vs HC. Unpaired t test and Mann-Whitney test were applied. P value < 0.5 was taken as significance level.

Fig. 2. : VEGF in leprosy. (A) Circulating levels of VEGF in non-reactional leprosy patients (NR) vs healthy controls (HC); (B) immunohistochemical evaluation of VEGF in NR lesions compared to HC (p = 0.02); (C) VEGF-positive endothelial cells in NR leprosy lesions (400x magnification; Bar: 25 µM). Mann-Whitney test was applied. P value < 0.5 was taken as significance level.

Fig. 3. : tissue factor (TF) in leprosy. (A) Serum levels of TF in non-reactional leprosy (NR) showing a trend to statistical significance when compared to healthy controls (HC) (p = 0.06); (B) immunohistochemical data of TF in NR vs HC (p = 0.02); (C) TF immunostaining in endothelium of NR leprosy patients (400x magnification; Bar: 25 µM). Mann-Whitney test was applied. P value < 0.5 was taken as significance level.

Fig. 4. : thrombomodulin (TM) in type 1 leprosy reaction. (A) Serum levels of TM in type 1 reaction (T1R) compared to non-reactional leprosy (NRT1) (p = 0.02). (B) immunohistochemical findings of TM in T1R vs NRT1 (p = 0.06); (C-D) TM staining in T1R and NRT1 (400x magnification; Bar: 25 µM). Mann-Whitney test was applied. P value < 0.5 was taken as significance level.