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Growth and development in the haemopoietic system: the role of lymphokines and their possible therapeutic potential in disease and malignancy.

Some cells can produce soluble factors which modify the behaviour and/or growth pattern of other cells. These 'factors' are broadly referred to as cytokines and may be further classified on the basis of the cells which were first characterized as the producer cells. For example, lymphokines are the soluble products of lymphocytes and monokines are the soluble factors released by mononuclear phagocytes. Although useful, this nomenclature is in many respects misleading since protein sequence and gene structure analysis has shown that 'lymphokines' may not only be produced by lymphocytes, but by various other types of cells as well. Fortunately, with the advent of molecular techniques, the number of cytokines has decreased drastically and what was once an increasingly large number of factors is now becoming restricted to a manageable few. What remain, however, still pose conceptual and mechanistic problems. These have mainly arisen as a result of the assay systems used to detect and define the lymphokines and the problems in extending the findings to normal physiology. Almost exclusively, lymphocytes have been stimulated to produce and export their soluble factors in response to nonphysiologic stimuli, such as lectins, and the various lymphokines have been characterized on the basis of in vitro test systems. Therefore, for reasons which will become obvious later, many of the in vitro findings have been difficult to corroborate in in vivo situations. Nonetheless, the results obtained with these factors are sufficiently intriguing to warrant serious consideration regarding their relevance in normal haemopoiesis, their possible therapeutic potential and their involvement in disease.