Soluble cytokine receptor tumor necrosis factor

There is a relatively new, highly successful biological drug launched for the treatment of rheumatoid arthritis (RA). It was the only compound of a small company, Immunex. The drug is the soluble tumor necrosis factor receptor. Tumor necrosis factor (TNF) is a member of an important group of molecules called cytokines it is a highly potent promoter of the inflammatory response. 

Infliximab neutralizes the biological activity of tumor necrosis factor alpha (TNF ) by high-affinity binding to its soluble and transmembrane forms and inhibits TNF receptor binding. Infliximab does not neutralize TNF (lymphotoxin ), a related cytokine that uses the same receptors as TNF . 

H. Tilg, E. Trehu, M. B. Atkins, C. A. Dinarello, and J. W. Mier, Interleukin-6 (IL-6) as an Anti-Inflammatory Cytokine Induction of Circulating IL-1 Receptor Antagonist and Soluble Tumor Necrosis Factor Receptor p55, Blood. 8 (1994) 113-118. 

The authors speculated that the most likely explanation for these observations was linked to the lack of transfer of high-molecular weight soluble receptors and IgG across the blood-brain barrier, implying that control of brain tumor necrosis factor alfa cannot be obtained with monoclonal antibodies. They thought that neurological complications in diseases other than multiple sclerosis might be related to control of tumor necrosis factor alfa in the periphery, resulting in an enhanced contribution of brain-derived tumor necrosis factor alfa or other cytokines, such as interleukin-1. 

Olsson, L, Gatanaga, T., Gullberg, U., Lantz, M., and Granger, G. A. (1993). Tumor necrosis factor (TNF) binding proteins (soluble TNF receptor forms) with possible roles in inflammation and malignancy. Eur. Cytokine Network 4, 169-180. 

---