Cryoglobulins As Potential Triggers of Inflammation in Schizophrenia

Overview

Journal Schizophr Res Treatment

Publisher Wiley

Date 2014 Jan 24

PMID 24455252

Authors

Andranik Chavushyan

Meri Hovsepyan

Anna Boyajyan

Affiliations

Soon will be listed here.

Abstract

This case study aimed to investigate effects of type III cryoglobulins isolated from the blood of patients with schizophrenia on the production of proinflammatory cytokines interleukin(IL)-1 β , IL-6 and tumor necrosis factor- α (TNF- α ), anti-inflammatory cytokine IL-10, and chemotactic cytokines IL-8 and monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells (PBMCs). The experiments were performed in vitro using PBMCs healthy subjects and the blood of patients whit schizoprenia. The enzyme-linked immunosorbent assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay were used upon study. The results obtained indicated significant increase (P < 0.05) in IL-1 β , IL-6, TNF- α , IL-8, and MCP-1 production by cultured PBMCs when incubating for 24 hours with cryoglobulins, beginning from 0.4 mg/mL. The gender difference does not affect the cryoglobulins-induced production of these cytokines by PBMCs. No influence of cryoglobulins on production of IL-10 by PBMCs was observed. Also, it was shown that cryoglobulins in concentration ≤4 mg/mL possessed no cytotoxic effect towards cultured PBMCs. Based upon the results obtained, we concluded that type III cryoglobulins are implicated in schizophrenia-associated alterations in the immune response through induction of the expression of proinflammatory and chemotactic cytokines by PBMCs.

References

Di Nicola M, Cattaneo A, Hepgul N, Di Forti M, Aitchison K, Janiri L . Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun. 2012; 31:90-5. PMC: 3675681. DOI: 10.1016/j.bbi.2012.06.010. View

Mathsson L, Lampa J, Mullazehi M, Ronnelid J . Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-alpha by peripheral blood mononuclear cells. Arthritis Res Ther. 2006; 8(3):R64. PMC: 1526644. DOI: 10.1186/ar1926. View

Weiner S, Prasauskas V, Lebrecht D, Weber S, Peter H, Vaith P . Occurrence of C-reactive protein in cryoglobulins. Clin Exp Immunol. 2001; 125(2):316-22. PMC: 1906118. DOI: 10.1046/j.1365-2249.2001.01606.x. View

Denys A, Udalova I, Smith C, Williams L, Ciesielski C, Campbell J . Evidence for a dual mechanism for IL-10 suppression of TNF-alpha production that does not involve inhibition of p38 mitogen-activated protein kinase or NF-kappa B in primary human macrophages. J Immunol. 2002; 168(10):4837-45. DOI: 10.4049/jimmunol.168.10.4837. View

Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura G, Rossi G . Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. J Psychiatr Res. 2003; 37(6):457-62. DOI: 10.1016/s0022-3956(03)00072-4. View

Rothermundt M, Arolt V, Bayer T . Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun. 2002; 15(4):319-39. DOI: 10.1006/brbi.2001.0648. View

Brouet J, Clauvel J, DANON F, Klein M, SELIGMANN M . Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. 1974; 57(5):775-88. DOI: 10.1016/0002-9343(74)90852-3. View

Katila H, Appelberg B, Hurme M, Rimon R . Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders. Schizophr Res. 1994; 12(1):29-34. DOI: 10.1016/0920-9964(94)90081-7. View

Almoguera B, Riveiro-Alvarez R, Lopez-Castroman J, Dorado P, Lopez-Rodriguez R, Fernandez-Navarro P . ATA homozigosity in the IL-10 gene promoter is a risk factor for schizophrenia in Spanish females: a case control study. BMC Med Genet. 2011; 12:81. PMC: 3144450. DOI: 10.1186/1471-2350-12-81. View

10.

Kunz M, Cereser K, Goi P, Fries G, Teixeira A, Fernandes B . Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. Braz J Psychiatry. 2011; 33(3):268-74. DOI: 10.1590/s1516-44462011000300010. View

11.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

12.

Mathsson L, Tejde A, Carlson K, Hoglund M, Nilsson B, Nilsson-Ekdahl K . Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones. Br J Haematol. 2005; 129(6):830-8. DOI: 10.1111/j.1365-2141.2005.05538.x. View

13.

Klickstein L, Barbashov S, Liu T, Jack R, Nicholson-Weller A . Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity. 1997; 7(3):345-55. DOI: 10.1016/s1074-7613(00)80356-8. View

14.

Paul-Samojedny M, Kowalczyk M, Suchanek R, Owczarek A, Fila-Danilow A, Szczygiel A . Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. J Mol Neurosci. 2010; 42(1):112-9. DOI: 10.1007/s12031-010-9365-6. View

15.

Garcia-Bueno B, Bioque M, Mac-Dowell K, Fe Barcones M, Martinez-Cengotitabengoa M, Pina-Camacho L . Pro-/anti-inflammatory dysregulation in patients with first episode of psychosis: toward an integrative inflammatory hypothesis of schizophrenia. Schizophr Bull. 2013; 40(2):376-87. PMC: 3932081. DOI: 10.1093/schbul/sbt001. View

16.

Boyajyan A, Khoyetsyan A, Tsakanova G, Sim R . Cryoglobulins as indicators of upregulated immune response in schizophrenia. Clin Biochem. 2007; 41(6):355-60. DOI: 10.1016/j.clinbiochem.2007.11.014. View

17.

Muller N, Schwarz M . Immune System and Schizophrenia. Curr Immunol Rev. 2010; 6(3):213-220. PMC: 2971548. DOI: 10.2174/157339510791823673. View

18.

Ramos-Casals M, Stone J, Cid M, Bosch X . The cryoglobulinaemias. Lancet. 2011; 379(9813):348-60. DOI: 10.1016/S0140-6736(11)60242-0. View

19.

Takada S, Shimizu T, Hadano Y, Matsumoto K, Kataoka Y, Arima Y . Cryoglobulinemia (review). Mol Med Rep. 2012; 6(1):3-8. DOI: 10.3892/mmr.2012.861. View

20.

Miller B, Buckley P, Seabolt W, Mellor A, Kirkpatrick B . Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011; 70(7):663-71. PMC: 4071300. DOI: 10.1016/j.biopsych.2011.04.013. View