A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy

Abstract

Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern recognition receptors, such as toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs), are present in the innate immune system. Sen and Baltimore (1986) discovered the transcription factor nuclear factor kappa-B (NF-B), employed by eukaryotic cells to regulate immunity, cell differentiation and proliferation. This study aimed to evaluate the role of the nuclear factor kappa B (NF-B) pathway in controlling the cytokine cascade in leprosy due to a lack of understanding of the link between cytokines and the severity of leprosy. Clinically suspected Hansen’s patients were analysed for 4 years. Newly diagnosed leprosy patients were considered to have leprosy disease control (LDC). The cases with active or new lesions and an increase in BI by at least 2+, 12 months after completion of MDT were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (HC). An ELISA was performed to measure the concentration of five human cytokines. By qRT-PCR, the quantitative expression of receptor genes (NOD1 and NOD2), cytokine genes and the expression of the transcription factor NFκβ were evaluated. This was followed by a transcription factor NFκβ assay to see its expression in the monocytes of study subjects. Nuclear factor NF-κβ was found to have a pronounced response in monocytes of HC and LDC patients and LDR cases when treated with NOD1 and NOD2 ligands. Our study concludes that the NF-kB pathway is involved in the induction and regulation of the cytokine cascade that contributes to chronic inflammation in leprosy.