Cytokines and chemokines are pleiotrophic proteins that coordinate the host response to infection as well as mediate normal, ongoing communication between cells of non-immune tissues, including the nervous system [
27]. As a consequence of this dual role, cytokines induced in response to an adverse stimuli (i.e. maternal infection or prenatal hypoxia) can profoundly impact fetal neurodevelopment. Aberrant levels of proinflammatory cytokines, interleukin 6 (IL-6), TNF-α and monocyte chemotactic protein-1 (MCP-1), not only in brain specimens and cerebrospinal fluid (CSF; [
90,
101]) but also in amniotic fluid [
1], index an active inflammatory process both in children and adults with ASC. These molecules act to increase immune cell recruitment and proliferation. Immune pathways are activated by proinflammatory cytokines such as TNF-α and IL-6 that stimulate the nuclear translocation of various transcription factors, including NF-κB that subsequently results in the potentiation of the immune response [
81]. This is tightly controlled in acute infection and lasts for a limited time. However, the presence of such molecules in the absence of an acute stimulus is an atypical response. An atypical inflammatory response has been observed in peripheral samples to show similar changes [
56] as well as decreases in anti-inflammatory protein IL-10 [
56]. In a larger multi-analyte profiling (MAP) analysis, Suzuki et al. [
98] reported from a total of 48 analytes examined, the plasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17, and growth regulated oncogene-alpha (GRO-α) were significantly higher in individuals with ASC compared with the corresponding values of matched controls, after correction for multiple comparisons. Upregulation of inflammation-related molecules has also been found to be characteristic for adult males (but not females) with Asperger syndrome [
95]. In mid-gestation maternal serum, elevated concentrations of IFN-γ, IL-4, and IL-5 were significantly associated with a 50 % increased risk of ASC, regardless of ASC onset type and the presence of intellectual disability [
45].
The main issue surrounding the reporting of serum results is that they show considerable within- and between-group variability. As such, the subtle differences found may indicate the presence of separate subgroups of the condition [
60]. For example, statistical clustering analysis on large-scale clinical data suggests the presence of subgroups with ASC characterised by co-occurrence of infectious disorder [
31], which could be related to physiological atypicality related to inflammatory processes. Further analysis using appropriately powered studies will be required in order to gauge the potential explanatory power of this hypothesis.