Modulatory influence of unsaturated fatty acids on the biology of tumour necrosis factor-alpha.

Introduction The cytokine tumour necrosis factor (TNF) is one of a diverse range of molecules that play a major part in inducing and modulating inflammatory and immune processes. TNF, in common with other cytokines, is predominantly a product of the immune system; however, endothelial cells also have the capabilty of its production. Biologically, TNF acts as a trigger that activates a cascade of cytokine production. The molecule is released rapidly in response to inflammatory and infective agents and induces production of a wide range of cytokines, including interleukins 1 and 6 (IL-1 and 11,-6) with which it has a number of actions in common. These include fever, free radical and acute phase protein production and up-regulation of adhesion molecules [ 1-31. TNF may prolong the inflammatory process by inducing the chemokine IL-8 [4]. TNF can indirectly modulate immunological events by induction of IL-1, which stimulates IL-2 and IL-4 production. The latter two cytokines result in increased lymphocyte proliferation and switching of immunoglobulin classes respectively [4]. In addition to its important role as an early effector in inflammatory and immune processes, TNF is important in the killing of fungi and a number of viruses [S]. However, excessive or biologically inappropriate TNF production is closely associated with pathological events. Such events have been closely linked with mortality from cerebral malaria, endotoxic shock, sepsis and adult respiratory distress syndrome, and with pathology in a wide range of autoimmune disorders [ 11. These include rheumatoid arthritis, inflammatory bowel disease, psoriasis