TLR4 and rheumatoid arthritis: However, research related to rheumatoid arthritis demonstrated that the expression of Toll-like receptor 4 (TLR4) and TNF-α, but also of IL-10, are HIF-1-dependent processes in macrophages, indicating that IVD-infiltrating immune cells may be more affected by the hypoxic microenvironment than IVD cells themselves (Guo and Chen, 2020).