Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1.
A number of cytokines contribute to acute experimental neurodegeneration. The cytokine response can have detrimental or beneficial effects depending on the temporal profile and balance between pro- and anti-inflammatory molecules. Our recent data suggest that the pro-inflammatory cytokine interleukin-1beta (IL-1beta) acts at specific sites (e.g., the striatum) in the rat brain to cause distant cortical injury, when co-administered with the potent excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA). The objective of the present study was to investigate changes in the expression of several cytokines simultaneously in the rat striatum and cortex after intrastriatal administration of vehicle, S-AMPA or human recombinant (hr) IL-1beta alone or S-AMPA co-injected with hrIL-1beta using reverse transcription-polymerase chain reaction (RT-PCR; Taqman fluorogenic probes) and enzyme-linked immunosorbent assay (ELISA). Injection of S-AMPA alone increased IL-6 mRNA expression in the ipsilateral striatum after 8 h, whilst striatal injection of IL-1beta alone increased local IL-1beta and IL-1ra mRNAs. The levels of mRNA encoding IL-1alpha, IL-1beta, IL-1ra, IL-6, IL-10 and TNFalpha were markedly elevated in the ipsilateral cortex 8 h after co-injection of S-AMPA and hrIL-1beta. Cortical mRNA levels for IL-4, IL-18, TGFbeta and IFNgamma were not significantly different between treatment groups after 2 h or 8 h. A similar pattern of change in the levels of IL-1alpha and IL-6 protein was observed 8 h after treatment. These data demonstrate selective increases in the expression of cytokines in areas of remote cell death in response to administration of hrIL-1beta and S-AMPA. Such cytokines may be involved in the ensuing damage, and further clarification of their actions could aid future therapeutic strategies for several acute neurodegenerative disorders.