Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia.
BACKGROUND
The pleiotropic pro-inflammatory cytokine Interleukin (IL)-18 has been proposed to play a role in schizophrenia, since elevated circulating levels of its protein and altered frequencies of genetic variants in its molecular system are reported in schizophrenic patients.


METHODS
We analyzed 77 patients with schizophrenia diagnosis (SCZ) and 77 healthy control subjects (HC) for serum concentration of both IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP).


RESULTS
We confirmed that serum levels of total IL-18 are significantly increased in SCZ, as compared to HC. However, due to a highly significant increase in levels of circulating IL-18BP in SCZ, as compared to HC, the levels of free, bioactive IL-18 are not significantly different between the two groups. In addition, the relationships between the levels of IL-18 and its inhibitor, as well as between the two molecules and age appear dissimilar for SCZ and HC. In particular, the elevated levels of IL-18BP, likely a consequence of the body's attempt to counteract the early prominent inflammation which characterizes schizophrenia, are maintained in earlier and later stages of the disease. However, the IL-18BP elevation appears ineffective to balance the IL-18 system in younger SCZ patients, while in older patients the levels of circulating bioactive IL-18 are comparable to those of HC, if not lower.


CONCLUSIONS
In conclusion, these findings indicate that the IL-18 system is perturbed in schizophrenia, supporting the idea that this pro-inflammatory cytokine might be part of a pathway of genetic and environmental components for vulnerability to the disease.
Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy.
Ilaria
I
Palladino
Francesca
F
Salani
Antonio
A
Ciaramella
Ivo Alex
IA
Rubino
Carlo
C
Caltagirone
Sabrina
S
Fagioli
Gianfranco
G
Spalletta
Paola
P
Bossù
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood* / Q000453:epidemiology; D055815:Young Adult
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein