Immunity and inflammation play a very important role in many diseases, including autism.

 Immune dysfunction in autism: 

“Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment.” (Careaga et al. Neurotherapeutics 2010) There are many reports of cytokine imbalances in autism spectrum disorders (ASD). These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity but they also have significant interactions with the nervous system. Cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Ashwood et al. (Brain Behav Immun. 2011) reported on significant increases in plasma levels of a number of cytokines, including IL-1β, IL-6, IL-8 and IL-12p40 in the ASD group compared with controls. Suzuki et al. (PLoS One 2011) reported that the plasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-α were significantly higher in subjects with ASD compared with the corresponding values of matched controls. Okada et al. (Prog Neuropsychopharmacol Biol Psychiatry 2007) and Ashwood et al. (J Neuroimmunol. 2008 ) reported on decreased serum levels of transforming growth factor- beta1 (TGFb1) in patients with autism, with lower TGFb1 levels associated with lower adaptive behaviors and worse behavioral symptoms, suggesting that immune responses in autism may be inappropriately regulated due to reductions in TGFb1.

Elevated serum levels of interleukin-17 (IL-17) in children with autism

CD4-positive T lymphocytes play a major role in the regulation of adaptive immunity. Upon activation by antigen-presenting cells (APC), naive antigen-specific CD4+ T cells differentiate into different subsets of T cells. In addition to the classic T-helper (Th)1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. Th17 CD4 T cells are characterized by production of the cytokines interleukin (IL)-17A (IL-17) and IL-17F, and IL-21 and IL-22. Since their discovery in 2003, there have been numerous studies on Th17 cells, and they have emerged as key players in the pathogenesis of some autoimmune neuroinflammatory diseases and other autoimmune disorders traditionally attributed to Th1 cells. Children with autism had significantly higher serum.

Live Borrelia activates IL1-Beta gene expression

Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1,8 and the IL-1 receptor antagonist (IL-lra) in human pe- ripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1l@ than IL-la and sevenfold more IL-1l8 than IL-lra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1,B was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains.

Activation of Human Monocytes by Live Borrelia

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete’s outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-b and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling.

Mast cell activation and autism

Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins. A number of papers, mostly based on parental reporting on their children’s health problems, suggest that ASD children may present with “allergic-like” problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation.