A number of different
cytokines, each initially characterized on the basis of very different
biological activities, all have very similar signalling pathways and share a similar tertiary structure. These
cytokines include leukaemia inhibitory
factor, ciliary neuronotrophic factor,
oncostatin M, growth-promoting activity and
cardiotrophin 1. They all have been found to regulate a number of properties of cells of the developing and mature nervous system in vitro and thus are neuroregulatory
cytokines. The actions of these
cytokines include regulation of
neurotransmitter phenotype, differentiation of neuronal precursor cells both in the peripheral nervous system and in the spinal cord, survival of differentiated neurons, and regulation of development of both astrocytes and oligodendrocytes. In addition, studies in animal models show that these factors can rescue sensory and motor neurons from
axotomy-induced cell death, which suggests that they can act as
trauma factors for injured neurons. Analysis of the expression patterns of the different neuroregulatory
cytokines and their receptors reveals that the receptors are expressed throughout nervous system development and following
trauma, whereas the
cytokines show temporal and spatial specific expression patterns. This is consistent with the idea that specific
cytokines have specific roles in neural development and repair, but that their signalling pathways are shared. The phenotypes of the receptor knockouts show clear deficits in nervous system development, indicating a crucial role for LIF receptor signalling. Knockouts of individual
cytokines are less dramatic, but LIF and
CNTF knockouts do reveal deficits in maintenance of motor neurons or following
trauma. Thus, whereas LIF and
CNTF have clear roles in maintenance and following
trauma, it is unclear which of the
cytokines is involved in nervous system development. In clinical terms, these findings add further support to the use of these
cytokines in
nervous system trauma and disease.