Since the 1970s, scientists have known that autism is influenced by immunologic factors. However, though it seems clear that immune dysfunction plays a role in this multi-factorial disorder, no specific cause of autism has been identified to date.
One compelling area of research is the study of cytokines. Cytokines, which are produced by specialized white blood cells, are molecules that serve as messengers within the immune system; they control a wide array of immune responses.
Some cytokines stimulate the immune system to respond to a perceived threat; others are inhibitory in nature, and serve to “turn down” an up-regulated immune system when a threat has been addressed. Ideally, these opposing actions help to maintain balance in a perennially challenging immunologic environment.
Cytokines are critical participants in both the innate immune system (present from birth; the first line of defense against all invaders; distinguishes what is “us” from what is “not us”) and the adaptive immune system (“learned” immune defenses in response to specific invading substances; develops throughout life; serves to “remember” past exposures).
Recently, researchers have discovered some interesting and relatively consistent abnormalities in the levels of cytokines in the brains and bloodstreams of children with autism.
Loss of Cytokine Balance in Autistic Children
Dr. Cynthia Molloy, at Cincinnati Children’s Hospital Medical Center, has demonstrated that the immune cells of autistic children are more highly activated than those of non-autistic children. In autism, the levels of both activating and suppressing cytokines are higher than normal, indicating a possible hypersensitivity to environmental exposures.
Oddly, however, Dr. Molloy discovered that the levels of interleukin-10 (IL-10), a critical inhibitory cytokine, were actually lower than expected in the same study subjects. This indicates a failure in the immune system’s regulatory, or balancing, function. (Journal of Neuroimmunology, May 27, 2006)
Abnormal Cytokine Response in Autistic Children
In a May 2005 study released at the 4th International Meeting for Autism Research, Drs. Judy Van de Water and Paul Ashwood from the University of California, Davis, showed that cells from autistic children exhibited abnormal cytokine responses to a variety of agents.
When challenged with tetanus toxoid, bacterial antigens, plant allergens, and a preparation of the mumps, measles, and rubella vaccine (MMR), the immune cells from autistic children responded in markedly different patterns than cells from control subjects. These findings lend credence to the hypothesis that children with underlying immune dysfunction can respond atypically to environmental stimuli.
Brain Inflammation in Autism
Scientists at Johns Hopkins University have shown that certain cells in the brains of many autistic children are abnormally active. Microglia and astroglia are cells that produce pro- and anti-inflammatory cytokines in their usual day-to-day function. They support nerve conduction and normal neuronal development.
In autistic children, these neuroglial cells produce cytokines in an unbalanced fashion. This can lead to inflammatory changes in the brain, which in turn can affect development and behavior. (Ann Neurol. 2005 Jan;57(1):67-81)
It is known that cytokines affect mood and behavior. One fascinating aspect of this function is the so-called “fever effect.” When autistic children fall ill and develop a fever, they sometimes exhibit a transient normalization in their behavior—some scientists have described this as a “surfacing” or “emerging” phenomenon.
Although the exact causes of autism remain tantalizingly out of reach, further research into the actions of cytokines such as IL-10, Transforming Growth Factor, or transfer factors may one day lead to effective means of treatment and prevention.
