Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker

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.

Apremilast in multibacillary leprosy patients with chronic and recurrent erythema nodosum leprosum: a prospective single‐centre pilot study

“…Apremilast downregulates inflammatory mediators including IFN-c, IL-2 and IL-6 that are involved in pathogenesis of ENL. 7,8 All patients in our study responded to the treatment within 30 days, and 6 out of 9 patients (66.6%) were in remission with no relapse of ENL for the remaining study period. Two steroid-dependent young females, who had developed cushingoid features and osteoporosis, could be tapered off prednisolone.…”

Diagnostic Value of Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in the Diagnosis of Erythema Nodosum Leprosum: A Retrospective Study

“…Elevated platelet count was observed in ENL patients, especially in the early phase of the disease [ 19 , 20 ]. One of the important mediators of thrombocytosis, interleukin-6, is also elevated during the initial phase of ENL [ 21 ].…”

Authors’ reply

“…We thank the authors of the letter 1 for their interesting comments on our article. 2 We developed this study to evaluate serum levels of some mediators involved in the innate and adaptative immune response of leprosy patients with erythema nodosum leprosum, since this reaction leads to severe peripheral nerve damage and physical incapacity as well as pain and malaise that deprive patients from social and economic interactions. Thus, the identification of possible serum immunomarkers for erythema nodosum leprosum could open new strategies for treatment and prevention, avoiding or reducing the nerve damage that impairs severely the quality of life of leprosy patients.…”