A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients.
Interleukin-1 (IL-1) mediates psychological stress responses by regulating monoamine metabolism and secretion of corticotropin-releasing factor, and is therefore, implicated in various psychiatric diseases. To evaluate the contribution of IL-1 signaling to the brain pathology of schizophrenia, we measured protein and/or mRNA levels for IL-1beta and endogenous IL-1 receptor antagonist (IL-1RA) in the postmortem brain tissues of prefrontal and parietal cortex, putamen, and hypothalamus. Both protein and mRNA levels of IL-1RA were specifically decreased in the prefrontal cortex of schizophrenic patients, whereas IL-1beta levels were not significantly altered in all the regions examined. The IL-1RA decrease was not correlated with the dose of antipsychotics given to patients. There was no influence of this illness on protein levels for IL-1 receptor type 1 in the prefrontal cortex, either. In contrast, IL-1RA serum levels were increased in schizophrenic patients, especially in drug-free patients, as reported previously. These findings suggest that chronic schizophrenia down-regulates IL-1RA production the prefrontal cortex, irrespective of its impact on the periphery. IL-1RA reduction might reflect an immunopathologic trait of the prefrontal region in schizophrenic patients.
Toyooka
Kazuhiko
K
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, 951-8585, Niigata, Japan.
Watanabe
Yuichiro
Y
Iritani
Shuji
S
Shimizu
Eiji
E
Iyo
Masaomi
M
Nakamura
Ryosuke
R
Asama
Koue
K
Makifuchi
Takao
T
Kakita
Akiyoshi
A
Takahashi
Hitoshi
H
Someya
Toshiyuki
T
Nawa
Hiroyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007118:Immunoassay; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000378:metabolism; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000032:analysis* / Q000097:blood / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D012795:Sialoglycoproteins