Interleukin-1 participates in the classical and alternative activation of microglia/macrophages after spinal cord injury

Background: microglia and macrophages (mg/mφ) have a diverse range of functions depending on unique cytokine stimuli,and contribute to neural cell death,repair,and remodeling during central nervous system diseases. while il-1 has been shown to exacerbate inflammation,it has also been recognized to enhance neuroregeneration. we determined the activating phenotype of mg/mφ and the impact of il-1 in an in vivo spinal cord injury (sci) model of il-1 knock-out (ko) mice. moreover,we demonstrated the contribution of il-1 to both the classical and alternative activation of mg in vitro using an adult mg primary culture.methods: sci was induced by transection of the spinal cord between the t9 and t10 vertebra in wild-type and il-1 ko mice. locomotor activity was monitored and lesion size was determined for 14 days. tnfα and ym1 levels were monitored to determine the mg/mφ activating phenotype. primary cultures of mg were produced from adult mice,and were exposed to ifnγ or il-4 with and without il-1β. moreover,cultures were exposed to il-4 and/or il-13 in the presence and absence of il-1β.results: the locomotor activity and lesion area of il-1 ko mice improved significantly after sci compared with wild-type mice. tnfα production was significantly suppressed in il-1 ko mice. also,ym1,an alternative activating mg/mφ marker,did not increase in il-1 ko mice,suggesting that il-1 contributes to both the classical and alternative activation of mg/mφ. we treated primary mg cultures with ifnγ or il-4 in the presence and absence of il-1β. increased nitric oxide and tnfα was present in the culture media and increased inducible no synthase was detected in cell suspensions following co-treatment with ifnγ and il-1β. expression of the alternative activation markers ym1 and arginase-1 was increased after exposure to il-4 and further increased after co-treatment with il-4 and il-1β. the phenotype was not observed after exposure of cells to il-13.conclusions: we demonstrate here in in vivo experiments that il-1 suppressed sci in a process mediated by the reduction of inflammatory responses. moreover,we suggest that il-1 participates in both the classical and alternative activation of mg in in vivo and in vitro systems. © 2012 sato et al; licensee biomed central ltd.