Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6.
Cytokines are thought to be important mediators in physiologic and pathophysiologic processes affecting the central nervous system (CNS). To explore this hypothesis, transgenic mice were generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS. A number of transgenic founder mice and their offspring exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression. Transgenic mice with high levels of IL-6 expression developed severe neurologic disease characterized by runting, tremor, ataxia, and seizure. Neuropathologic manifestations included neuro-degeneration, astrocytosis, angiogenesis, and induction of acute-phase-protein production. These findings indicate that cytokines such as IL-6 can have a direct pathogenic role in inflammatory, infectious, and neurodegenerative CNS diseases.
Campbell
I L
IL
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Abraham
C R
CR
Masliah
E
E
Kemper
P
P
Inglis
J D
JD
Oldstone
M B
MB
Mucke
L
L
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins