Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with multiple roles in the immune system. It is secreted mainly by macrophages and has a number of effects on the immune system, acting mainly in a paracrine fashion:

• activates macrophages and neutrophils
• acts as costimulator for T cell activation
• key mediator of bodies response to Gram negative septicaemia
• similar properties to IL-1
• anti-tumour effect (e.g. phospholipase activation)

TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce apoptosis. It also cause activation of NFkB

Endothelial effects include increase expression of selectins and increased production of platelet activating factor, IL-1 and prostaglandins

TNF promotes the proliferation of fibroblasts and their production of protease and collagenase. It is thought fragments of receptors act as binding points in serum

Systemic effects include pyrexia, increased acute phase proteins and disordered metabolism leading to cachexia

TNF inhibitors

TNF is important in the pathogenesis of a number of inflammatory conditions such as rheumatoid arthritis and Crohn's disease. TNF inhibitors are therefore now used for a variety of conditions.

Examples of TNF inhibitors

• infliximab: monoclonal antibody, IV administration
• etanercept: fusion protein that mimics the inhibitory effects of naturally occurring soluble TNF receptors, subcutaneous administration
• adalimumab: monoclonal antibody, subcutaneous administration
• golimumab: subcutaneous administration
• adverse effects of TNF blockers include reactivation of latent tuberculosis and demyelination

Infliximab is also used in active Crohn's disease unresponsive to steroids