CYTOKINE THERAPEUTICS - LESSONS FROM INTERFERON-ALPHA

Cytokines are soluble proteins that allow for communication between ce lls and the external environment. Interferon (IFN) alpha, the first cy tokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunologic al control. This review focuses on the biological and clinical activit ies of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogen ic, inflammatory, and fibrotic diseases suggests a spectrum of interre lated pathophysiologies. The principles learned from in vivo studies w ill be discussed, particularly hairy cell leukemia, chronic myelogenou s leukemia, certain angiogenic diseases, and hepatitis. After the surp rising discovery of activity in a rare B-cell neoplasm, IFN-alpha emer ged as a prototypic tumor suppressor protein that represses the clinic al tumorigenic phenotype in some malignancies capable of differentiati on. Regulatory agencies throughout the world have approved IFN-alpha f or treatment of 13 malignant and viral disorders. The principles estab lished with this cytokine serve as a paradigm for future development o f natural proteins for human disease.