The neuropoietic cytokine family in development, plasticity, disease and injury

Key Points Neuropoietic cytokines have a crucial role in nervous system development. Leukaemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have historically been associated with the development of astrocytes from neural stem and progenitor cells. With the discovery that some astrocytes are neurogenic, the potential of these cytokines to promote the development of astrocytes versus neural stem cells is being re-investigated. Cardiotrophin 1, but not LIF or CNTF, is involved in the temporal switch from neurogenesis to gliogenesis during nervous system development. Exogenous LIF stimulates mouse embryonic stem cell self-renewal in vitro , and adult neural stem cell self-renewal in vivo in the uninjured brain. Because endogenous LIF is transiently induced after many types of injury to the nervous system, LIF might be involved in progenitor cell recruitment after brain injury and could be used to promote brain repair. Neuropoietic cytokines are crucial in the response to injury. In certain settings they can act as trophic factors promoting survival and regeneration of injured axons. However, they are also intimately linked with inflammatory responses and reactive gliosis after injury, which can have negative consequences for neuronal survival and axon regeneration. While these cytokines might prove to be effective therapeutic tools to promote neuronal and oligodendrocyte survival in CNS diseases such as amyotrophic lateral sclerosis and multiple sclerosis, their ability to stimulate inflammatory and glial responses must be carefully monitored in order to limit unwanted side effects. IL-6 is implicated in long-term potentiation. These effects could occur through direct effects of interleukin-6 (IL-6) on neuronal excitability and through the regulation of Ca 2+ influx. A role for IL-6 in learning and memory is supported by cognitive tests. In animal models, LIF modulates the hypothalamic–pituitary–adrenal axis response to stress, and both LIF and IL-6 induce depression-like behaviours. In humans, IL-6 could have a role in symptoms of fatigue, asthenia and anorexia in major depression and bipolar disorder. LIF, CNTF and IL-6 are involved in feeding behaviour and control of body weight. There are also indications that members of this cytokine family can regulate sleep, motor activity patterns, aggression and social interaction. Neuropoietic cytokines are not only important in the immune system. Patterson and colleagues review their wide-ranging f