A differential role for interleukin-6 and tumor necrosis factor-α in schizophrenia?

Naudin, Jean; Capo, Concetta; Giusano, B; Mège, Jean Louis; Azorin, Jean‐Michel

doi:10.1016/s0920-9964(97)00059-5

Cited by 132 publications

(78 citation statements)

References 27 publications

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“…13,[41][42][43] Many components of the immune system have been studied for their roles in the disease, including IL2, 13,44 IL6 45,46 and TNF-a. 47 We have reported that IL3 is associated with schizophrenia and the associations observed are sex-specific and FHdependent. 3 Others report the association of IL3RA.…”

Section: Discussionmentioning

confidence: 99%

Association study of CSF2RB with schizophrenia in Irish family and case – control samples

et al. 2007

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Colony stimulating factor 2 receptor, beta (CSF2RB) is the shared subunit of receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2) and IL5, and is responsible for the initiation of signal transduction triggered by ligand binding. In our previous study, we showed the evidence that the IL3 gene is associated with schizophrenia and the associations observed are sex-specific and dependent on family history (FH). In this article, we studied 10 singlenucleotide polymorphisms in the CSF2RB gene in the Irish Study of High-Density Schizophrenia Families (ISHDSF) and the Irish Case -Control Study of Schizophrenia (ICCSS), and tested allele and haplotype associations with schizophrenia. Using the pedigree disequilibrium test, we found that two markers (rs11705394 and rs7285064) reached nominal significance. In sex-stratified analyses, for both the markers the association signals were mainly derived from male subjects. In the ICCSS sample, we found that several markers (rs2072707, rs2284031 and rs909486) showed sex-specific and FH-dependent associations with schizophrenia. In multimarker haplotype analyses, both ISHDSF and ICCSS samples showed globally significant associations in multiple linkage disequilibrium (LD) blocks sharing minimal LD. Since CSF2RB is essential for IL3 signaling, the findings that both IL3 and CSF2RB showed sex-specific and FH-dependent associations suggest that the IL3 pathway is involved in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Association study of CSF2RB with schizophrenia in Irish family and case – control samples

et al. 2007

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“…1,2 Significant increases in plasma concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-6 receptor (IL-6R), tumor necrosis factor ␣ (TNF␣) and interleukin-1 receptor antagonist (IL-1RA), as well as in cerebrospinal fluid levels of interleukin-2 (IL-2) have been reported in schizophrenic patients. [3][4][5][6][7] Cytokines are actively transported through the bloodbrain barrier, but they are also released by activated astrocytes and microglial cells. 20 It is now well established that cytokines can interact with neural cell functions, directly acting as messengers or influencing neurotransmitters and neuropeptide balance.…”

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Association between −G308A tumor necrosis factor alpha gene polymorphism and schizophrenia

et al. 2000

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Dysregulation of the inflammatory response system has been linked to pathophysiology of schizophrenia. 1,2 Evidence of immune activation has derived from the detection of abnormal levels of proinflammatory cytokines and their receptors in peripheral blood and cerebrospinal fluid from schizophrenic patients. 3-7 Cytokines are involved in normal CNS development as well as in the pathogenesis of many neuro-psychiatric disorders, acting directly on neural cells or modulating neurotransmitter and neuropeptide systems. 8,9 In particular tumor necrosis factor ␣ (TNF␣), depending on its concentration, can exert both neurotrophic and neurotoxic effects and influence neural cell growth and proliferation. 10,11 Moreover, TNF␣ gene is located on the small arm of chromosome 6 (6p21.1-21.3), a locus associated with genetic susceptibility to schizophrenia. 12, 13 We studied the distribution of −G308A TNF␣ gene polymorphism in 84 schizophrenic patients and in 138 healthy volunteers. This biallelic base exchange polymorphism directly affects TNF␣ plasma levels. 14-18 Frequency of the TNF2(A) allele is significantly increased in schizophrenic patients as compared to controls (P = 0.0042). Genotype distribution is also significantly different (P = 0.0024). TNF2 homozygotes are represented only in the patient group (P = 0.002). These data suggest a potential role of TNF␣ as a candidate gene for susceptibility to schizophrenia and suggest that immune dysregulation in schizophrenic patients could also have a genetic component. Molecular Psychiatry (2001) 6, 79-82.

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“…Schizophrenic patients have varied levels of proinflammatory cytokines, such as interleukin (IL)-1,-6, and tumor necrosis factor (TNF)␣ in their peripheral blood or cerebrospinal fluid. [1][2][3][4][5][6] These cytokines can modify the metabolism of neurotransmitters, influence neural development, and IL-1 has been implicated in acute, and, on the other hand, chronic neurodegeneration. were somewhat, but not significantly, higher in the schizophrenic patients as compared to the controls.…”

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confidence: 99%

“…[1][2][3][4][5][6] We recently demonstrated that plasma IL-1␤ levels were increased in a group of acute first admission drug-free schizophrenic patients as compared to healthy controls. 3 Others have linked elevated IL-6 and TNF-␣ levels to the course, the treatment or progression of schizophrenic illness.…”

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confidence: 99%

Polymorphisms of the interleukin-1 gene complex in schizophrenia

1999

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Activation of the inflammatory response system has been related to the pathophysiology of schizophrenia by several recent studies. Schizophrenic patients have varied levels of proinflammatory cytokines, such as interleukin (IL)-1,-6, and tumor necrosis factor (TNF)␣ in their peripheral blood or cerebrospinal fluid. [1][2][3][4][5][6] These cytokines can modify the metabolism of neurotransmitters, influence neural development, and IL-1 has been implicated in acute, and, on the other hand, chronic neurodegeneration. were somewhat, but not significantly, higher in the schizophrenic patients as compared to the controls. These alleles are known to be located on the same haplotype. 10 The number of carriers of this haplotype was significantly higher in the schizophrenia patients (17/50 vs 81/400) than in the controls (P = 0.026, 2 ). The frequencies of this haplotype were 0.38 and 0.27, respectively (P = 0.0266, 2 ). The number of homozygotes of this haplotype was significantly higher in the schizophrenia patients (P = 0.0006, 2 ). These data suggest that the cytokine aberrations in schizophrenia are, at least partly, genetically determined.

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A differential role for interleukin-6 and tumor necrosis factor-α in schizophrenia?

Cited by 132 publications

References 27 publications

Association study of CSF2RB with schizophrenia in Irish family and case – control samples

Association study of CSF2RB with schizophrenia in Irish family and case – control samples

Association between −G308A tumor necrosis factor alpha gene polymorphism and schizophrenia

Polymorphisms of the interleukin-1 gene complex in schizophrenia

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