Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide

Abstract

Background: Depression and stress are major risk factors for suicidal behaviour, and some studies show abnormalities of proinflammatory cytokines in the serum and cerebrospinal fluid (CSF) of depressed and suicidal patients. However, it is not clear if similar abnormalities of cytokines are present in the brain of suicidal and depressed patients.

Methods: We therefore determined the mRNA (using realtime polymerase chain reaction) and protein (using enzyme-linked immunosorbent assay and Western Blot) expression levels of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α, lymphotoxin A, lymphotoxin B, IL-8, IL-10 and IL-13 in the prefrontal cortex (PFC) obtained from 24 depressed individuals who died by suicide and 24 nonpsychiatric controls.

Results: We observed that the mRNA and protein levels of IL-1β, IL-6, TNF-α, and lymphotoxin A were significantly increased, and levels of anti-inflammatory cytokine IL-10, and of IL-1 receptor antagonist (IL-1RA) were significantly decreased in the PFC of depressed individuals who died by suicide compared with controls. There were no significant differences in the protein and mRNA levels of IL-8 and IL-13 in the PFC.

Limitations: The main limitation of this study is that some of the suicide group had been taking antidepressant medication at the time of death.

Conclusion: Our results suggest that alterations of cytokines may be associated with the pathophysiology of depressed suicide and there may be an imbalance between pro- and anti-inflammatory cytokines in people who die by suicide. The causes of these increases in the brain of people who die by suicide, therefore, need to be investigated further.

Fig. 1

Mean mRNA expression levels of inflammatory cytokines, including tumour necrosis factor (TNF)-α, lymphotoxin A (LTA), lymphotoxin B (LTB), interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1RA), IL-8, IL-10, and IL-13, in the prefrontal cortex (PFC) of depressed individuals who died by suicide (DS) and nonpsychiatric controls (NC). The data are shown as the fold change in mRNA levels ± standard error of the mean. *p < 0.05.

Fig. 2

Representative Western blots showing the immunolabelling of interleukin (IL)-1 receptor antagonist (IL-1RA), lymphotoxin A (LTA), lymphotoxin B (LTB), IL-8, IL-10, IL-13 and β-actin in the prefrontal cortex membrane fraction of 2 nonpsychiatric controls (NC) and 2 depressed individuals who died by suicide (DS).

Fig. 3

(A) Mean protein expression levels (pg/mg tissue) of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 and (B) percent of control of lymphotoxin A (LTA), lymphotoxin B (LTB), IL-1 receptor antagonist (IL-1RA), IL-8, IL-10 and IL-13 in the prefrontal cortex of depressed individuals who died by suicide (DS) and nonpsychiatric controls (NC). Values are given as the mean ± standard deviation. *p < 0.05.