Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome

Brain, Behavior, and Immunity

Volumn 25, Issue 1, 2011, Pages 40-45

  Ashwood, Paul ^a,c   Krakowiak, Paula ^a   Hertz Picciotto, Irva ^a,c   Hansen, Robin ^a,c   Pessah, Isaac ^b,c   Van de Water, Judy ^b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Autism; Behavior; Cytokines; Immunology; Regression

Indexed keywords

CYTOKINE; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 10; INTERLEUKIN 12P40; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 8; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; AUTISM; BEHAVIOR DISORDER; BLOOD SAMPLING; CHILD; CHILD DEVELOPMENT; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DEVELOPMENTAL DISORDER; DISEASE ASSOCIATION; FEMALE; HUMAN; IMMUNE DYSREGULATION; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL;

CHILD BEHAVIOR; CHILD BEHAVIOR DISORDERS; CHILD DEVELOPMENT DISORDERS, PERVASIVE; CHILD, PRESCHOOL; COMMUNICATION; CYTOKINES; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; FEMALE; HUMANS; MALE; NEUROPSYCHOLOGICAL TESTS; REGRESSION ANALYSIS;

EID: 78649322790     PISSN: 08891591     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbi.2010.08.003     Document Type: Article

References (48)

1. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR, fourth edition. American Psychiatric Association Publishing Inc., Washington DC, USA.
2. Ashwood P., Anthony A., Pellicer A.A., Torrente F., Walker-Smith J.A., Wakefield A.J. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J. Clin. Immunol. 2003, 23:504-517.
3. Ashwood P., Anthony A., Torrente F., Wakefield A.J. Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J. Clin. Immunol. 2004, 24(6):664-673.
4. 3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J. Neuroimmunol. 2006, 173(1-2):126-134.
5. Ashwood P., Enstrom A., Krakowiak P., Hertz-Picciotto I., Hansen R.L., Croen L.A., Ozonoff S., Pessah I.N., Van de Water J. Decreased transforming growth factor β1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J. Neuroimmunol. 2008, 204(1-2):149-153.
6. Ashwood P., Kwong C., Hansen R., Hertz-Picciotto I., Croen L., Krakowiak P., Walker W., Pessah I.N., Van de Water J. Plasma leptin levels are elevated in autism: association with early onset phenotype?. J. Autism Dev. Disord. 2008, 38(1):169-175.
7. Ashwood, P., Nguyen, D.V., Hessl, D., Hagerman, R.J., Tassone, F. in press. Plasma cytokine profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis? Brain Behav. Immun.
8. Barker V., Middleton G., Davey F., Davies A.M. TNFα contributes to the death of NGF-dependent neurons during development. Nat. Neurosci. 2001, 4(12):1194-1198.
9. Bu B., Ashwood P., Harvey D., King I.B., Van de Water J., Jin L.W. Fatty acid composition of red blood cell phospholipids in children with autism. Prostaglandins Leukot. Essent. Fatty Acids 2006, 74(4):215-221.
10. Cacci E., Ajmone-Cat M.A., Anelli T., Biagioni S., Minghetti L. In vitro neuronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Glia 2008, 56(4):412-425.
11. Cabanlit M., Wills S., Goines P., Ashwood P., Van de Water J. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann. N. Y. Acad. Sci. 2007, 1107:92-103.
12. Connolly A.M., Chez M., Streif E.M., Keeling R.M., Golumbek P.T., Kwon J.M., Riviello J.J., Robinson R.G., Neuman R.J., Deuel R.M. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol. Psychiatry 2006, 59(4):354-363.
13. Corbett B.A., Kantor A.B., Schulman H., Walker W.L., Lit L., Ashwood P., Rocke D.M., Sharp F.R. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Molecular Psychiatry 2007, 12(3):292-306.
14. Croonenberghs J., Bosmans E., Deboutte D., Kenis G., Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology 2002, 45(1):1-6.
15. Enstrom A., Onore C., Hertz-Picciotto I., Hansen R., Croen L., Van de Water J., Ashwood P. Detection of IL-17 and IL-23 in plasma samples of children with autism. Am. J. Biochem. Biotechnol. 2008, 4:114-120.
16. Enstrom A., Onore C., Tarver A., Hertz-Picciotto I., Hansen R., Croen L., Van de Water J., Ashwood P. Peripheral blood leukocyte production of BDNF following mitogen stimulation in early onset and regressive autism. Am. J. Biochem. Biotechnol. 2008, 4(2):121-129.
17. Enstrom A.M., Van de Water J.A., Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs 2009, 10:463-473.
18. Enstrom A., Krakowiak P., Onore C., Pessah I.N., Hertz-Picciotto I., Hansen R.L., Van de Water J.A., Ashwood P. Increased IgG4 levels in children with autism disorder. Brain Behav. Immun. 2009, 23:389-395.
19. Enstrom A.M., Lit L., Onore C.E., Gregg J.P., Hansen R.L., Pessah I.N., Hertz-Picciotto I., Van de Water J.A., Sharp F.R., Ashwood P. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav. Immun. 2009, 23(1):124-133.
20. Enstrom A., Onore C., Van de Water J., Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav. Immun. 2010, 24(1):64-71.
21. Gadient R.A., Patterson P.H. Leukemia inhibitory factor, interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury. Stem Cells 1999, 17(3):127-137.
22. Garbett K., Ebert P.J., Mitchell A., Lintas C., Manzi B., Mirnics K., Persico A.M. Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis 2008, 30(3):303-311.
23. Gilmore J.H., Jarskog L.F., Vadlamudi S. Maternal poly I:C exposure during pregnancy regulates TNFα, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat. J. Neuroimmunol. 2005, 159(1-2):106-112.
24. Grigorenko E.L., Han S.S., Yrigollen C.M., Leng L., Mizue Y., Anderson G.M., Mulder E.J., de Bildt A., Minderaa R.B., Volkmar F.R., Chang J.T., Bucala R. Macrophage migration inhibitory factor and autism spectrum disorders. Pediatrics 2008, 122(2):438-445.
25. Gupta S., Aggarwal S., Rashanravan B., Lee T. Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J. Neuroimmunol. 1998, 85(1):106-109.
26. Hansen R.L., Ozonoff S., Krakowiak P., Angkustsiri K., Jones C., Deprey L.J., Le D.N., Croen L.A., Hertz-Picciotto I. Regression in autism: prevalence and associated factors in the CHARGE Study. Ambul Pediatr 2008, (1):25-31.
27. Hertz-Picciotto I., Croen L.A., Hansen R., Jones C.R., Van de Water J., Pessah I.N. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ. Health Perspect. 2006, 114:1119-1125.
28. Juttler E., Tarabin V., Schwaninger M. Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 2002, 8:268-275.
29. Jyonouchi H., Geng L., Ruby A., Zimmerman-Bier B. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology 2005, 51(2):77-85.
30. Li X., Chauhan A., Sheikh A.M., Patil S., Chauhan V., Li X.-M., Ji L., Brown T., Malik M. Elevated immune response in the brain of autistic patients. J. Neuroimmunol. 2009, 207(1-2):111-116.
31. Mehler M.F., Kessler J.A. Cytokines in brain development and function. Adv. Protein Chem. 1998, 52:223-251.
32. MMWR Surveill. Summ, 2009. Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators; Centers for Disease Control and Prevention (CDC). 58 (10): 1-20.
33. Molloy C.A., Morrow A.L., Meinzen-Derr J., Schleifer K., Dienger K., Manning-Courtney P., Altaye M., Wills-Karp M. Elevated cytokine levels in children with autism spectrum disorder. J. Neuroimmunol. 2006, 172(1-2):198-205.
34. Munoz-Fernandez M.A., Fresno M. The role of tumour necrosis factor, interleukin 6, interferon-γ and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog. Neurobiol. 1998, 56(3):307-340.
35. Okada K., Hashimoto K., Iwata Y., Nakamura K., Tsujii M., Tsuchiya K.J., Sekine Y., Suda S., Suzuki K., Sugihara G., Matsuzaki H., Mori N. Decreased serum levels of transforming growth factor-β1 in patients with autism. Prog. Neuropsychopharmacol. Biol. Psychiatry 2007, 31(1):187-190.
36. Onore C., Krakowiak P., Enstrom A., Hansen R., Hertz-Picciotto I., Van de Water J., Ashwood P. Decreased cellular IL-23 production in children with autism spectrum disorders. J. Neuroimmunol. 2009, 216(1-2):126-129.
37. Saresella M., Marventano I., Guerini F.R., Mancuso R., Ceresa L., Zanzottera M., Rusconi B., Maggioni E., Tinelli C., Clerici M. An autistic endophenotype results in complex immune dysfunction in healthy siblings of autistic children. Biol. Psychiatry 2009, 66(10):978-984.
38. Shi L., Fatemi S.H., Sidwell R.W., Patterson P.H. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J. Neurosci. 2003, 23(1):297-302.
39. Singh V.K., Warren R.P., Odell J.D., Cole P. Changes of soluble interleukin-2, interleukin-2 receptor, T 8 antigen, and interleukin-1 in the serum of autistic children. Clin. Immunol. Immunopathol. 1991, 61(3):448-455.
40. Singh V.K. Plasma increase of interleukin-12 and interferon-γ. Pathological significance in autism. J. Neuroimmunol. 1996, 66(1-2):143-145.
41. Silva S.C., Correia C., Fesel C., Barreto M., Coutinho A.M., Marques C., Miguel T.S., Ataide A., Bento C., Borges L., Oliveira G., Vicente A.M. Autoantibody repertoires to brain tissue in autism nuclear families. J. Neuroimmunol. 2004, 152(1-2):176-182.
42. Sweeten T.L., Posey D.J., Shankar S., McDougle C.J. High nitric oxide production in autistic disorder: a possible role for interferon-γ. Biol. Psychiatry 2004, 55(4):434-437.
43. Todd R.D., Hickok J.M., Anderson G.M., Cohen D.J. Antibrain antibodies in infantile autism. Biol. Psychiatry 1988, 23(6):644-647.
44. Tsuchiya K.J., Hashimoto K., Iwata Y., Tsujii M., Sekine Y., Sugihara G., Matsuzaki H., Suda S., Kawai M., Nakamura K., Minabe Y., Yagi A., Iyo M., Takei N., Mori N. Decreased serum levels of platelet-endothelial adhesion molecule (PECAM-1) in subjects with high-functioning autism: a negative correlation with head circumference at birth. Biol. Psychiatry 2007, 62:1056-1058.
45. Vargas D.L., Nascimbene C., Krishnan C., Zimmerman A.W., Pardo C.A. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 2005, 57(1):67-81.
46. Vojdani A., Campbell A.W., Anyanwu E., Kashanian A., Bock K., Vojdani E. Antibodies to neuron-specific antigens in children with autism: Possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. J. Neuroimmunol. 2002, 129(1-2):168-177.
47. Wills S., Cabanlit M., Bennett J., Ashwood P., Amaral D.G., Van de Water J. Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain Behav. Immun. 2009, 23(1):64-74.
48. Zimmerman A.W., Jyonouchi H., Comi A.M., Connors S.L., Milstien S., Varsou A., Heyes M.P. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr. Neurol. 2005, 33(3):195-201.