TNF and viral infectious disease: The classical activated macrophages (pro-inflammatory M1) mediate the pro-inflammatory response and promote the T helper type 1 (Th1)-polarized immune response against bacterial, protozoan, and viral infections by producing copious inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and inducible nitric oxide synthase (iNOS).