Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression

We determined innate and adaptive immune responses in children with develop mental regression and autism spectrum disorders (ASD, N = 71), developmenta lly normal siblings (N = 23), and controls (N = 17). With lipopolysaccharid e (LPS), a stimulant for innate immunity, peripheral blood mononuclear cell s (PBMCs) from 59/71 (83.1%) ASD patients produced > 2 SD above the control mean (CM) values of TNF-alpha, IL-1 beta, and/or IL-6 produced by control PBMCs. ASD PBMCs produced higher levels of proinflammatory/counter-regulato ry cytokines without stimuli than controls. With stimulants of phytohemaggl utinin (PHA), tetanus, IL-12p70, and IL-18, PBMCs from 47.9% to 60% of ASD patients produced > 2 SD above the CM values of TNF-alpha depending on stim ulants. Our results indicate excessive innate immune responses in a number of ASD children that may be most evident in TNF-alpha production. (C) 2001 Elsevier Science B.V. All rights reserved.