linked to demyelination of neurons. In melanoma cell lines, IL-10 modulates the surface expression of NKG2D ligands. In addition, Forkhead box protein 3 (Foxp3) as a transcription factor is an essential molecular marker of regulatory T (Treg) cells. Foxp3 polymorphism (rs3761548) might be involved in cancer progression like gastric cancer through influencing Tregs function and the secretion of immunomodulatory cytokines such as IL-10, IL-35, and TGF-β. A recent mouse study indicates that IL-10 regulates CD36, a key phagocytosis effector, promoting hematoma clearance after intracerebral hemorrhage. IL-10 deficiency aggravates traumatic brain injury in male but not female mice. Clinical use or trials Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. and, indeed, patients with Crohn's disease react favorably towards treatment with recombinant interleukin-10-producing bacteria, demonstrating the importance of IL-10 for counteracting the hyperactive immune response in the human body. Due to the data, thousands of patients with a variety of autoimmune diseases were treated with recombinant human IL-10 (rHuIL-10) in clinical trials. Contrary to expectations, rHuIL-10 treatment did not significantly impact disease in patients with Crohn's disease or rheumatoid arthritis. rHuIL-10 treatment initially exhibited promising clinical data in psoriasis, but failed to achieve clinical significance in a randomized, double blind, placebo controlled Phase II trial. Further investigation of rHuIL-10's effects in humans suggests that rather than inhibiting inflammation, rHuIL-10 is capable of exerting pro-inflammatory effects. PEGylated forms Further to these data, a Phase I immunoncology clinical trial is currently being conducted to assess the therapeutic capacity of PEGylated recombinant human IL-10 (PEG-rHuIL-10, AM0010). Consistent with preclinical immunoncology data, investigators report substantial anti-tumor efficacy. Contrary to the reported immunosuppressive effects of IL-10 generated in vitro and in vivo, treatment of cancer patients with PEG-rHuIL-10 elicits a dose titratable induction of the immune stimulatory cytokines IFNγ, IL-18, IL-7, GM-CSF and IL-4. Furthermore, treated patients exhibit fold increases of peripheral CD8+ T cells expressing markers of activation, such as programmed death 1 (PD1)+, lymphocyte activation gene 3 (LAG3)+ and increased Fas Ligand (FasL) and a decrease in serum TGFβ. These findings are consistent with the published preclinical immunoncology reports using PEG-rMuIL-10 and with previous findings treating humans with rHuIL-10. These data suggest that while IL-10 can exert immunosuppressive effects in context of bacterial product stimulated myeloid cells, rHuIL-10/PEG-rHuIL-10 treatment of humans is predominantly immunostimulatory. AM0010 (aka pegilodecakin) is in phase 3 clinical trials. Interactions