Immunosuppression is frequently accompanied by the attraction of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), M2 tumor-associated macrophages (TAMs), T regulatory cells (Tregs), N2 neutrophils, and by the release of immunosuppressive cytokines (TGF-β, IL-10) and chemokines.
Gradually increasing amounts of ascites were correlated significantly, even after correction for FIGO stage, with reduced survival (p<0.0001) and stronger immunosuppression (IL10 and VEGF).
<b>Results:</b> MCAo resulted in profound attenuation of immune activation, as anticipated. t-PA treatment not only worsened neurological deficit, but further reduced lymphocyte and monocyte counts in blood, enhanced plasma levels of both IL-10 and TNFα and decreased various conventional DC subsets in the spleen and cLN, consistent with enhanced immunosuppression and systemic inflammation after stroke.
The main predisposition of PMN formation in melanoma lies in the pulmonary recruitment of granulocytic myeloid-derived suppressor cells (G-MDSCs, CD11b<sup>+</sup>Ly6G<sup>+</sup> cells) induced by tumors, which increase vascular permeability by secreting matrix metalloproteinase-9 (MMP-9) and result in immunosuppression by secreting interleukin-10 (IL-10) in premetastatic lungs.
Random amino acid copolymers used in the treatment of multiple sclerosis in man or experimental autoimmune encephalomyelitis (EAE) in mice [poly(Y,E,A,K)<sub>n</sub>, known as Copaxone, and poly(Y,F,A,K)<sub>n</sub>] function at least in part by generation of IL-10-secreting regulatory T cells that mediate bystander immunosuppression.
The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival.
In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1β-deficient mice, IL-12 secretion by CD11b<sup>+</sup> DCs prevails and supports antitumor immunity.
These results support that IL-10 drives the molecular path that generates MDSCs and enhances immunosuppression during late sepsis, and inform that targeting this immune repressor path may improve sepsis survival in mice.
The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion).
A growing number of studies reveals that micro- and nano-particles can cause exaggerated and persistent immunosuppression characterized by the release of potent anti-inflammatory cytokines (IL-10 and TGF-β), and the recruitment of major regulatory immune cells (M2 macrophages, T and B regs, and MDSC).
On the other hand, Dex inhibited the secretion of Th2 cytokines (IL-10 in Dex/Af group: 5.27 ± 0.85 pg/ml; control/Af group: 15.14 ± 1.40 pg/ml, t = 14.761, P < 0.001)), and successfully caused immunosuppression.
Tumor-induced immunosuppression is mediated through various mechanisms including engagement of immune checkpoint receptors on effector cells, function of immunoregulatory cells such as regulatory T cells and myeloid-derived suppressor cells, and deployment of immunosuppressive cytokines such as TGFβ and IL10.
Biochemical and functional analyses show that adenosine, but not typical suppressive factors such as PD-L1, CTLA-4, TGF-β, IL-35, and IL-10, contributes to apoptotic T<sub>reg</sub>-cell-mediated immunosuppression.
Expression of the anti-inflammatory cytokine IL-10 was increased in endometrial tissues, while expression of the pro-inflammatory cytokine IL-6 was decreased, indicating immunosuppression.