Endotoxin tolerance modulates TREG and TH17 lymphocytes protecting septic mice

Abstract

<b>Background</b>: Tolerance induces a regulated immune response to infection. We hypothesized that tolerance induction modulated profile of T regulatory cell (Treg) and T lymphocyte 17 (Th17) cells and is related cytokine released in septic animals. <b>Methods</b>: Male black <i>C57/6 mice</i> received subcutaneous (s.c.) injections of lipopolysaccharide (LPS) (1 mg/kg) for 5 days, on day 8^th was made cecal ligation and puncture (CLP). Blood and spleen tissue were collected for cell analysis and cytokines measurements. <b>Results</b>: Cytokines (interleukin 2 (IL-2), interleukin (IL-6), transforming growth factor β (TGF-β) and interferon γ (INF-γ)) related to Treg and Th17 stimulation were elevated in the spleen of tolerant animals compared to sham. Treg and Th17 lymphocytes showed an increased amount in blood (Treg: 920 ± 84 cells vs. 1946 ± 65 cells, sham vs. tolerant; Th17:38321± 1954 cells vs. 43526 ± 7623 cells, sham vs. tolerant) and spleen (Treg: 5947 ± 273 cells vs. 16521 ± 486 cells, sham vs. tolerant; Th17: 26543 ± 2944 cells vs. 64567 ± 5523 cells, sham vs. tolerant). Treg (135±23 cells) and Th17 (1590 ± 256 cells) cells were reduced in blood of septic animals compared to sham, while CLP tolerant animals presented an increasing number of these cells. Lymphocyte Th17IL6+ were elevated in tolerant and CLP tolerant animals in the blood compared to sham. <b>Conclusion</b>: LPS tolerance was associated with increasing population of Treg and Th17. LPS tolerance reduces the hyper inflammatory response with immunoregulation exerted by Treg and Th17 cells protecting from septic damage.