Both TGF-β and IL-10 have immune suppression effects to downregulate secretion and release of inflammatory factors, such as TNF-α, that play roles in regulating osteoblast and osteoclast functions.
An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation.
We reported here that asparaginase disturbed the function of macrophages including phagocytosis, proliferation, ROS and nitric oxide secretion, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) secretion, and major histocompatibility complex II (MHC-II) molecule expression, thus induced immune suppression in interferon-γ and lipopolysaccharide-stimulated macrophages.
The presence of regulatory T cells, the inhibition of natural killer cytotoxic responses, the accumulation of myeloid suppressor cells in the tumor, deficiencies on interferon signaling, the secretion of cytokines that enhance tumor growth (i.e., IL-6, IL-10, CSF-1, TGF-b, TNF), and the expression of surface molecules (i.e., HLA-G, B7-H1, B7-H4, CD40, CD80) that have a role on immune suppression, are discussed in detail.
Systemic delivery of soluble TNF receptors or other antagonists may have deleterious side effects associated with immune suppression, so that strategies for locally targeted drug delivery are of interest.
Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine capable of activating T and dendritic cells (DCs) and counteracting IL-10-mediated DC inhibition and regulatory T-cell-mediated immune suppression.