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Yet, there are limitations, beyond the excessive pricing that became popular with the new compounds: TNF is strictly required for the control of bacterial and fungal infections by neutrophils and for granuloma formation in order to control infections with mycobacteria and many other pathogens [3–7] . The role of TNF antagonists in viral diseases and human cancer remains under debate [11] . IL-12 is a key cytokine for interferon-dependent defense mechanisms, such as viral diseases, probably cancer, and again granuloma formation such as mycobacterial infections [9, 12, 13] . Moreover, cytokine antagonists may lose their efficiency; after about 1 year TNF antagonists remain effective in about 60% of patients, and the long-term effects and side effects ( 1 10 years) remain to be established. The difficulty in truly estimating the biology of cytokine antagonists is underlined by simple clinical observations: all TNF antagonists were developed with similar rational approaches. Clinical studies revealed that the effects of the various TNF antagonists on the various types of psoriasis, psoriasis arthritis, rheumatoid arthritis or inflammatory bowel disease differ strongly between these compounds – for unknown reasons [3–7] . Changing Psoriasis Therapy

Interleukin 4 or Cytokine Antagonists? Time to Change the Search for Novel Psoriasis Therapies