[14] IL-10 may autoregulate its expression via a negative feed-back loop involving autocrine stimulation of the IL-10 receptor and inhibition of the p38 signaling pathway.

[15] Additionally, IL-10 expression is extensively regulated at the post-transcriptional level, which may involve control of mRNA stability via AU-rich elements[16] and by microRNAs such as let-7[17] or miR-106.

[20][21][22][23] Further investigation has shown that IL-10 predominantly inhibits lipopolysaccharide (LPS) and bacterial product mediated induction of the pro-inflammatory cytokines TNFα,[24] IL-1β,[24] IL-12,[25] and IFNγ[26] secretion from toll-like receptor (TLR) triggered myeloid lineage cells.

Over time a more nuanced picture of IL-10's function has emerged as treatment of tumor-bearing mice has been shown to inhibit tumor metastasis.

[27] Additional investigation by multiple laboratories has generated data that further supports IL-10's immunostimulatory capacity in an immunoncology context.

[43] In addition, Forkhead box protein 3 (Foxp3) as a transcription factor is an essential molecular marker of regulatory T (Treg) cells.

[44] A recent mouse study indicates that IL-10 regulates CD36, a key phagocytosis effector, promoting hematoma clearance after intracerebral hemorrhage.

[47] 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.

[48] 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.

[55][56] 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).

[57] Contrary to the reported immunosuppressive effects of IL-10 generated in vitro and in vivo,[21][22][23][24][25] 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.

[55][56] 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.