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Interleukin 1 dependent cell loss after spinal cord injury (SCI)
Author(s) -
Nesic O.,
Svrakic N. M.,
Xu G.Y.,
McAdoo D.,
Westlund K. N.,
Hulsebosch C. E.,
PerezPolo R. J.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.41_5.x
Subject(s) - apoptosis , spinal cord injury , programmed cell death , spinal cord , receptor , interleukin 1 receptor antagonist , receptor antagonist , cytokine , caspase , biology , medicine , pharmacology , immunology , neuroscience , antagonist , biochemistry
We hypothesized that blocking receptors for pro‐inflammatory cytokine, interleukin‐1 (IL‐1) would ameliorate SCI‐dependent cell loss and resulting motor dysfunction. We found that chronic administration of recombinant IL‐1 receptor antagonist (rIL‐1ra) reduced SCI‐induced increases in cell death markers and caspase‐3 activity, suggesting that IL‐1ra prevents apoptosis in injured spinal cords. We also found that IL‐1ra significantly improved locomotor recovery. To answer the question how is the inhibition of IL‐1 receptors preventing cell death in injured spinal cord and improving motor recovery, we analyzed transcriptional changes in injured vs. injured spinal cord treated with IL‐1ra, via DNA microarrays. We found a large number of mRNAs whose expression levels were significantly changed after SCI and reversed in the presence of IL‐1ra. For example, we found that iNOS and COX‐2 mRNA are significantly up‐regulated after injury and down‐regulated in IL‐1ra‐treated spinal cords. If iNOS and COX‐2 proteins are synthesized, it is very likely that their activity will produce reactive oxygen species (ROS), which will cause cell death via different converging apoptotic pathways. We also found that SCI induces IL‐1 dependent up‐regulation of pro‐apoptotic cathepsins and cell cycle regulators, a novel finding. Therefore, we hypothesize that the anti‐inflammatory IL‐1ra could be therapeutic and alleviate secondary damage after SCI. Acknowledgements: Supported in part by grant NS39161 from NINDS and Mission Connect Foundation.