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NFκB activation in cutaneous lesions of leprosy is associated with development of multibacillary infection

Abstract
Background: Nuclear factor kappa B (NFkB) transcription factors play a central role in controlling the expression of genes involved in inflammatory reactions, proliferation, and survival of human cells. However, the in situ evaluation of NFkB activity in leprosy has not been completed previously. The aim of this study was to determine whether NFkB activity correlates with susceptibility or resistance to Mycobacterium leprae infection in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy. Methods: The NFkB activation profile was evaluated in biopsies from skin lesions of 38 patients with the clinical and laboratory diagnosis of leprosy. NFkB activation was evaluated and quantified by Southwestern histochemistry, and its activation index (range, 0–4) was calculated according to the percentage of nuclear positivity by the histochemistry. Activation index .1 was considered representative of activation of NFkB. Results: Fifteen patients (39.5%) demonstrated activated NFkB. Multibacillary leprosy was associated with activated NFkB (54.5%, P=0.028). Borderline leprosy was most strongly associated with NFkB activation (80%), with an odds ratio of 32.7 (P=0.016). These clinical forms are characterized by increased susceptibility to M. leprae and by immunological instability. Activation of NFkB was absent in the granulomas in tuberculoid leprosy, which represents an effective inflammatory reaction pattern against M. leprae. Conclusion: These results indicate that NFkB activation could favor susceptibility and immunological instability to M. leprae infection, potentially by the stimulation of phagocytosis and the regulation of apoptotic mechanisms of infected cells, leading to the proliferation of this intracellular bacillus. Further studies are needed to evaluate if inhibition of NFkB activation in multibacillary leprosy could favor resistance and an effective granulomatous immune response.

More information

Type
Journal Article
Author
Wambier C
Ramalho L
Foss N
Frade MA
Year of Publication
2014
Journal
Journal of Inflammation Research
Number of Pages
133
Language
eng
DOI
10.2147/JIR10.2147/JIR.S62562
Alternate Journal
J Inflamm Res
Publication Language
eng