[Basis of cytokines--history and present status]

Cytokines are high molecular-weight substances which actively promote homeostasis and defend from exogenous agents. In 1965, Kasakura, et al, and Gordon, et al independently published articles describing an unknown substance (blastogenic factor) which was produced in the cultured media of lymphocytes and stimulated lymphocytic proliferation. In those days, since almost all immunologists believed that only antigens stimulated lymphocytic proliferation, the idea that this soluble factor actually had a positive role in lymphocytic proliferation was viewed suspiciously. Later, it was found that immune responses are constructed of mutual intercellular stimulations between T and B lymphocytes and macrophages. In the 1970s, several kinds of cytokines were found. Cytokines include lymphokines and monokines. These were named for substances produced from lymphocytes and monocytes, respectively. In 1972, at the second lymphokine workshop in Switzerland, a new term, "interleukin", was accepted as the name of an active substance which reacts mutually among leukocytes. Specific interleukins (IL) are numbered, e.g. IL-1, 2, 3 and so on. Later, a new term, BRM (biological responsive modifiers), was added to denote substances including not only cytokines but also other high weight molecules acting on various kinds of cells and tissues. Among the various kinds of cytokines, CSF (colony stimulating factor), Epo (erythropoietin), IL, TNF, and interferon are well known. In particular, CSF and Epo have been widely used for granulopenia and renal anemia with remarkable effects.