Eicosanoid and cytokine levels differentiate between stages of MTB infection

Introduction: The need for biomarkers predicting the course of MTB infection and the necessity of specific therapy are well recognized. Recent data point to the role of cytokines and lipid mediators in protective immunity against tuberculosis. Aim: We evaluated the balance between cytokines, and eikosanoids as a possible prognostic indicator in MTB infection. Material and methods: The induced expression of effector and regulatory cytokines IFN-γ, TNF-α, IL-2, IL-17, IL-6, and IL-10 was measured in relation to the lipid mediators PGE2 and LXA4 in active TB infection (ATB, n=15) before and after therapy (ATB-T, n=6), established latent infection (LTBI, n=22), recent contacts of ATB (RC, n=12), and healthy controls (n=11) A flow cytometry microarray (CBA, BD Biosciences) and quantitative ELISA (SunRed Tech) were employed. Results: The regulatory cytokines (RC) were characterized by a high potential for IL-17 and Th1 cytokine secretion, combined with low IL-6 expression, while ATB donors had a partially preserved TNF-α potential, and higher IL-6 expression. The PGE2-to-LXA4 ratio discriminated between situations with high bacterial load (ATB), and contained infection (LTBI, ATB-T), and defined clearly cut subgroups among RC and ATB donors. Conclusions: Our results suggest that increased PGE2/LXA4 ratio coupled with high induced IL-10 level indicates infection after a recent contact. In the settings of ATB, increased ratio and low TNF-α level point to inefficient granuloma formation in the settings of ATB.