Differential expression of interleukin-6 in leprosy reactions.
28 Aug 2021-Indian Journal of Dermatology, Venereology and Leprology (Indian J Dermatol Venereol Leprol)-pp 1-2
About: This article is published in Indian Journal of Dermatology, Venereology and Leprology.The article was published on 2021-08-28 and is currently open access. It has received None citations till now. The article focuses on the topics: Interleukin 6.
TL;DR: This review focuses on recent advances in the understanding of M. leprae and the host response to it, especially concerning molecular identification of M.'s genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis.
Abstract: Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases.
TL;DR: IL-6 appears to be the only major cytokine elaborated by mycobacteria-infected PMs, in vitro, and thus may function as a potent biomarker of myc Cobacterial infection, either stand-alone or along with other cytokines.
Abstract: Background Human tuberculosis (TB), a chronic inflammatory disease is caused by Mycobacterium tuberculosis, a facultative intramacrophage pathogen. The highly complex interactions between mycobacteria and macrophages (MΦs), characterized in part by the induction and elaboration of several cytokines including IL-1, IL-6, IL-10, IL-12 p40 and IL-12 p70 are not yet fully understood. The cytokines are known to have important bearing on the pathogenesis and host defense during TB. We thus studied different patterns of cytokines elaborated by mouse peritoneal macrophages (PMs) following their interaction with live and heat-killed, virulent and avirulent, and pathogenic and non-pathogenic mycobacteria, in vitro.
TL;DR: The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases.
Abstract: Background 50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.
TL;DR: Two nested case-control studies were built from a cohort of 409 patients with leprosy from central Brazil, monitored for T1R and T2R, and evidence for association between T 2R and IL-6 tag single-nucleotide polymorphisms was found.
Abstract: In leprosy, type 1 reaction (T1R) and type 2 reaction (T2R) are major causes of nerve injury and permanent disabilities. A previous study on plasma levels of 27 cytokines in patients with T1R or T2R and controls with nonreactional leprosy identified the gene for interleukin 6 (IL-6) as a candidate for genetic analysis. Two nested case-control studies were built from a cohort of 409 patients with leprosy from central Brazil, monitored for T1R and T2R. There was evidence for association between T2R and IL-6 tag single-nucleotide polymorphisms rs2069832 (P 5 .002), rs2069840 (P 5 .03), and rs2069845 (P 5 .04), with information on the entire IL-6 locus, as well as functional IL-6 variant rs1800795 (P 5 .005). Moreover, IL-6 plasma levels in patients with T2R correlated with IL-6 genotypes (P 5 .04). No association was found between IL-6 variants and T1R. Identifying genetic predictive factors for leprosy reactions may have a major impact on preventive strategies.
TL;DR: In this paper, the authors evaluated selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for Erythema nodosum leprosum (ENL).
Abstract: Background Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. Aims The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. Methods The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). Results Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. Limitations Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. Conclusion High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.