TNF and rheumatoid arthritis: For example, in patients with chronic RA, clear signs of M1 activity, such as high levels of pro-inflammatory or regulatory cytokines, growth factors (e.g., IL-1, IL-6, IL-13, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF)), chemokines, and chemoattractants (e.g., IL-8) are evident in the synovial membrane [15].