Cytokines regulate IGF binding proteins in the cns

Growth factor induction is a major component of the response to central nervous system trauma. The insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) are among the molecules induced by injury that have demonstrated neuroprotective actions. Induction of IGFBPs 2, 3, 4 and 5 have been documented following injury and are hypothesized to function in transport or localization of the IGFs to injured cells. It is unclear what factors lead to induction of these molecules following trauma, however, several cytokines including ciliary neurotrophic factor (CNTF) and interleukin-1 beta (IL-1 beta) have been described as major injury signals and can induce aspects of reactive gliosis. To establish whether these cytokines also are responsible for inducing the IGFBPs following CNS injury, we injected CNTF or IL-1 beta intracerebrally into the neocortex of adult rats and measured changes in mRNA expression for the IGFBPs. IGFBP-2 mRNA showed a dramatic increase by 24-48 h following either CNTF or IL-1 beta injection as compared with the contralateral side injected with heat-inactivated cytokine. Neither CNTF nor IL-1 beta caused alterations in BP3 or BP5. Levels of BP4 and BP6 mRNAs also were unchanged following CNTF injection. These results suggest that IGFBP2 is uniquely regulated among the IGFBPs in the CNS and is induced by cytokines that signal CNS injury.