Abstract

Interleukin (IL)-10, a multifunctional immune-regulatory cytokine with both immunosuppressive and anti-angiogenic functions, is produced by immune cells including macrophages, T lymphocytes, and natural killer cells. Among other effects, IL-10 promotes tumor cell proliferation and metastasis via immunosuppression. Interleukin-10-mediated immunosuppression is aided by synthesis of tumor necrosis factor, IL-1, IL-12, and chemokines, and down regulation of the surface co-stimulatory molecules CD80 and CD86 on tumors. Interleukin-10 also promotes IL-6 expression and synthesis, which causes cell proliferation via B cell lymphoma-2 (Bcl-2) upregulation and changes the proliferation/apoptosis equivalence toward neoplastic cell proliferation. Moreover, IL-10 inhibits tumorigenesis via down-regulation of VEGF, IL-1b, TNF-α, IL-6, and MMP-9. Interleukin-10 also inhibits nuclear factor-KB (NF-KB) translocation. Interleukin-10 has been reported to have both tumor-promoting and -inhibiting properties. It seems that IL-10 agonists and antagonists may have therapeutic effects via different mechanisms. Moreover, IL-10 gene polymorphisms may determine breast cancer susceptibility.