IL-1RA injected intra-cisterna magna confers extended prophylaxis against lipopolysaccharide-induced neuroinflammatory and sickness responses

IL-1RA has been used intra-cerebrally to ameliorate neuroinflammatory responses. The present study explored the possibility that the bioactivity of IL-1RA administered intra-cerebrally may be prolonged in the CNS. hIL-1RA was detected in hippocampus from 2 h to 14 d post-ICM treatment. hIL-1RA ameliorated both the hippocampal cytokine (TNFα and NFκBIα) and sickness response to peripheral LPS administered 4 d after hIL-1RA. Four days post treatment, hIL-1RA reduced the basal expression of IL-1R1, Iba-1, MHCII, and TLR4 and blunted the microglial IL-1β and IL-6 response to LPS ex vivo. IL-1RA might be administered prophylactically to prevent the neuroinflammatory effects of trauma.