Monocytes chemoattractant protein-1 [MCP-1] and other proinflamatory cytokines in children with autism

ABSTRACT

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication, speech, repetitive behaviors, and social withdrawal. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. Cytokines are protein or peptide that include, interleukines, interferons, tumor necrosis factor and others. Cytokines can influence physiological functions such as sleep and food intake; they also interact with a number of neurotransmitters in the brain. Cytokines, and the immune system together, may play a very important role in the development of autism and there is now some evidence that autism may be accompanied by abnormalities in the inflammatory response system [IRS]. Products of the IRS, such as proinflammatory cytokines, may induce some of the behavioral symptoms of autism, such as social withdrawal, resistance to novelty and sleep disturbances. Thus, a potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from children with autism compared with age-matched control children. Was to evaluate, if autism is accompanied by an activation of the inflammatory response system, and to investigate whether immunemediated mechanisms are involved in the pathogenesis of autism or not through evaluation of the plasma levels of the proinflammatory cytokines as interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] in children with autism, and compare them with the age-matched healthy control children. This study was carried out in the Psychiatry Unit, Department of Pediatrics, Tanta University Hospital. Thirty children with prior diagnosis of autism[24 males, 6 females] were included in the study, their age range was[3-9 years]with the mean age of 5 +/- 1.8 years. Diagnosis of autism was based on the criteria for the diagnosis of autism that are set out in the Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR [Fourth Edition, Text Revision]. The intial Childhood Autism Rating Scale [CARS] score for these children was >/= 30, as children with a CARS score >/= 30 were considered to have autism. Intial CARS score range for children with autism was [31-60]. The control group consisted of thirty healthy children [10 females, 20 males]. Their age range was [2-10 years] and the mean age was 5.31 +/- 2.4 years. Plasma levels of the proinflammatory cytokines as interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] were evaluated for children with autism, and the control children. The mean plasma levels of the proinflammtory cytokines, interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] in children with autism, were significantly higher than the mean plasma levels of these proinflammatory cytokines in the control children [P<0.01]. In conclusion, Increased levels of plasma proinflammatory cytokines in children with autism, support the hypothesis that an abnormal immune response could be another component of this multifactorial disorder. These findings serve as further evidence that inflammation may be an important part of the pathogenesis of autism and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of autism