Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6

Sir:

Dr. Patterson’s group has elucidated a critical finding that supports the role of interleukin-6 (IL-6) in the pathogenesis of schizophrenia and autism in the context of maternal immune activation (Smith et al 2007). Extending the three mechanisms of action by IL-6 postulated by Smith et al (2007), I hypothesize that interaction between IL-6 and insulin systems (specifically Insulin-like Growth Factor-1 [IGF- 1]) might play a crucial role.

IGF-1 plays a significant role in fetal development (Fowden, 2003). Also, IGF-1 has neuroprotective, anti-apoptotic properties that are crucial for optimal development of the brain (Dore et al 1997). Interestingly, IL-6 inhibits the secretion of IGF-I and its biological activity (de Martino et al 2000; Lazarus et al 1993). Cerebral damage in fetal pro-inflammatory states has been associated with high IL-6 and low IGF-1 levels (Hansen-Pupp et al 2007). These studies support significant interaction between IL-6 and IGF-1.

Increased IL-6 (Potvin et al 2007) as well as deficient IGF-1 (Venkatasubramanian et al 2007) have been demonstrated in schizophrenia. Autism is also associated with higher IL-6 (Jyonouchi et al 2001) and lower IGF-1 (Riikonen et al 2006). Interestingly, maternal infection has been shown to increase the expression of fetal pro-inflammatory genes like IL-6 in the mouse (Liverman et al 2006). Hence, it is possible that maternal immune activation might result in persistent over-expression of IL-6 genes in human adolescents and adults, leading to deficient IGF-1 culminating in neurobehavioral disorders like schizophrenia and autism. In summary, this postulate of neuro-immuno-metabolic effects of IL-6 further supports the key observations reported by Smith et al (2007).

References

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