Attenuation of astroglial reactivity by interleukin-10.
Prominent responses that follow brain trauma include the activation of microglia, recruitment of blood-derived macrophages, and astroglial reactivity. Based on evidence that cytokines produced by macrophages/microglia may cause astrocytes to become reactive, the aim of this study was to determine whether astroglial reactivity could be attenuated by interleukin (IL)-10, a potent inhibitor of cytokine synthesis by macrophages/microglia. Four days after the local application of IL-10 to the site of corticectomy in adult mice, the number of reactive astrocytes and their state of hypertrophy was reduced (by 60%) when compared with vehicle controls. In the majority of IL-10-treated mice, but not in any vehicle controls, the tissue in the immediate vicinity of IL-10 application contained viable but non reactive astrocytes. The mechanism by which IL-10 attenuates astroglial reactivity is likely via the reduction of cytokine production by macrophages/microglia because, based on Mac-1 immunohistochemistry, the macrophages/microglia of IL-10 brains had a decreased activation state compared with vehicle-controls. Another macrophage/microglia deactivating agent, macrophage inhibitory factor, also reduced astroglial activity in vivo. Furthermore, IL-10 had no direct effect on purified astrocytes in culture, indicating that its in vivo action on astroglial reactivity is likely via indirect mechanisms. Finally, injury resulted in the substantial rise of tumor necrosis factor-alpha mRNA levels, and this elevation was significantly inhibited by IL-10. The ability to manipulate the extent of astrogliosis should provide a means of addressing the neurotrophic or inhibitory role of reactive astrocytes in neurological recovery.
Balasingam
V
V
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.
Yong
V W
VW
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001483:Base Sequence; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D008263:Macrophage Migration-Inhibitory Factors; D016177:Macrophage-1 Antigen; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10