Cyclooxygenase 2 and vascular endothelial growth factor–potential targets to manage lepra reactions: A case‐control study

Abstract

Reactions in leprosy have an immune mediated pathogenesis. While type 1 reactions are delayed hypersensitivity phenomenon, type 2 reactions are immune complex mediated. Key molecules which mediate the immune insult in lepra reactions require evaluation in order to tailor their therapy and prevent disability. The objective of the study was to evaluate expressions of Cyclooxygenase 2 and Vascular Endothelial Growth Factor in skin biopsies from leprosy patients and correlate their expression with presence of either type 1 or type 2 lepra reactions. This was a case control study. Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression in dermal macrophages and vascular endothelium was assessed immunohistochemically. Biopsies from patients with Non-reactive leprosy and healthy controls were used for comparison. SPSS software was used for statistical analysis. A total of 147 skin biopsies were evaluated, including 18 with Type 1 reaction, 39 Type 2 reaction, 81 non-reactive leprosy and 9 healthy controls. Both Cyclooxygenase 2 and Vascular Endothelial Growth Factor expression were significantly higher in type 1 followed by type 2 reaction as compared to controls. These results may guide us regarding use of Cyclooxygenase 2 and Vascular Endothelial Growth Factor inhibitor drugs which may be a major step in treating reactive leprosy patients and preventing nerve damage and disability.

Cyclooxygenase-2 as potential intervention target of leprosy reactions: a systematic review

“…22 But our review found that one study reveals VEGF is overexpressed in T1R 13 meanwhile another study found nondifference of VEGF in T1R compared to non-T1R. 15 Therefore, the role of COX-2 in T1R through this VEGF pathway is controversial.…”

“…Based on their treatment status, patients who were on medication had a higher risk of COX-2 expression than non-on-treatment patients (191.50 ± 56.76 vs 141.98 ± 78.85). 15 Genetic studies have also shown that the PTGS2 gene (central gene in the Arachnoid Acid Pathway) encoding COX-2 is up-regulated in T1R patients. In addition, the TNFAIP6 gene encodes TNFstimulated gene 6 (TSG6), whose function as an inducer of COX-2 expression in macrophages is also upregulated in earlyonset T1R.…”