CYTOKINES
If you look at most text books on Immunology, the definition of "cytokines" along with a list of the most well known cytokines often appears in the chapter on cell-mediated immunity (CMI) although "cytokines" are likely to be referred to in many different places within the text. This is because the early soluble mediators - the lymphocyte-derived mediators - were associated with CMI responses. It was only later when cells other than those of the immune system were found to release these factors that the cytokine concept developed.
IFN-a, also known as Type I interferon, was really the first of these soluble factors to be described. It was identified by Isaacs and Lindenmann in 1957 as a factor obtained from virally-infected chick chorioallantoic membranes that "interfered" with subsequent viral replication in uninfected cultures. The first of the lymphocyte-derived mediators, was described in 1965, when Wheelock reported that PHA could induce an interferon-like virus inhibitor substance in leukocyte cultures. This factor was subsequently called IFN-g.
For many immunologists, migration inhibition factor (MIF) was the first of what came to be known as lymphokines. This was an activity in supernatants from antigen-activated lymphocytes that inhibited the movement of macrophages in in vitro assays. It was identified simultaneously in 1966 by John David and Barry Bloom working in two separate laboratories. The next of the lymphocyte-derived factors to be described was lymphotoxin (LT) (Nancy Ruddle and Byron Waksman). Others followed and in 1969 Dudley Dumonde proposed the term "lymphokine" to described these factors. Subsequently, activities derived from macrophages and monocytes in culture were naturally called "monokines". These lymphokines and monokines were first described in antigen- or mitogen-activated cell cultures. Following the discovery of a lymphokine activity in virus-infected kidney cell cultures, it was suggested that that the various soluble substances represented a broad class of mediators of host defense secreted by cells and should more properly be called "cytokines".
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