Fever

Temperature is tightly controlled in warm-blooded animals. Neural, endocrine and immune mechanisms are called into play to maintain an internal temperature of between 98 F and 99 F over a wide range of external temperatures. For example, when core body temperature rises, blood vessels in the skin dilate, and vessels to internal organs constrict in order to dissipate heat.

The temperature set point is not fixed, however. In the face of a bacterial or viral invasion, core temperature rises. When it exceeds 99.5 F, it is called a fever, and a new set point is established at a higher level. Fever combats the infection by activating lymphocytes and other immune mechanisms.

Relevance to autism:

It has long been reported anecdotally that the symptoms of some children with autism improve when they have a fever. Often detailed enough to preclude simple wishful thinking, the reports began to appear in the 1980s and have continued since. In informal surveys of parents, approximately 30 to 40 percent of children with autism appear to improve when they have a fever.

In a 2007 study, the parents of 30 children with autism between 2 and 18 years of age filled out the Aberrant Behavior Checklist when their children had a fever above 100.4F, after the fever resolved and when the child had been fever-free for seven days1. Results of this study suggested that the children’s behavior — related to irritability, hyperactivity, repetitive behavior and inappropriate speech — improved when they had a fever compared with seven days post-fever.

A preliminary survey of families enrolled in the Simons Simplex Collection also indicates that as many as 25 percent of parents report some improvement when their children are febrile.

The mechanism involved in the transient fever effect is unknown. It has been suggested that the locus coeruleus plays a role in both the febrile response and the ameliorative process2.

Neurons in the LC connect widely to and receive projections from many regions in the brain, including areas of the hypothalamus directly involved in mediating the fever response.

Mechanism:

In April 2010, SFARI hosted a workshop to discuss fever’s role in autism.

It is not clear whether the mechanism underlying fever’s link to autism is related to the immune system or simply a rise in core body temperature, which has a powerful impact on neuronal functioning.

The firing of neurons in relevant neural circuits could be enhanced or suppressed by small changes in temperature. Neuronal firing might be also influenced by circulating chemicals such as prostaglandins (for example, PGE2) or one of the many circulating cytokines (for example, interleukin 6) that are synthesized and released to defend against invading organisms.

Maternal infection is a reported risk factor for autism-like symptoms in the offspring, and autism is associated with autoimmune disease and allergies in the mother.

Some studies have also found that people with autism have peripheral immune abnormalities, as well as dysregulation of immune-related genes in the brain, activated microglia and astrocytes, and an increase in cytokine levels in the brain and cerebrospinal fluid. The immune responses to peripheral infection could interact with the dysregulated immune system in an individual with autism, leading to altered behaviors.


References:
  1. Curran L. et al. Pediatrics 120:e1386-92 (2007) PubMed
  2. Mehler M.F. and D.P. Purpura Brain Res. Rev. 59, 388-392 (2009) PubMed