Does the Insulin‐Like Growth Factor System Interact with Prostaglandins and Proinflammatory Cytokines During Neurodegeneration?

Abstract

Abstract. Prostaglandins and proinflammatory cytokines are implicated in the etiology of neurodegenerative diseases, such as Alzheimer's disease. Signaling cascades initiated by these factors may result in reactive oxygen species generation and cell death. The insulin‐like growth factors (IGF) are ubiquitous polypeptides involved in all aspects of growth and development. Additionally, the IGF are regarded as survival factors that display potent antiapoptotic activity. Interfering with IGF production, distribution, or signaling may result in greater susceptibility to apoptotic stimuli. In neurodegenerative conditions, the IGF appear to be antagonized by prostaglandins and proinflammatory cytokines. In this review, the relationship among specific prostaglandins, the proinflammatory factors, tumor necrosis factor, interleukin‐1, and interleukin‐6, and the IGF system will be investigated.

Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence

“…In chronic inflammation an interaction between IGF-I and other cytokines (especially IL-6) has been suggested [ 45 ]. An interaction between cytokines and IGF-I in acute inflammation or sepsis and a reduction of IGF-I directly or indirectly thought TNF- α and/or IL-1 β has been reported [ 46 , 47 ].…”

The role of IGF-1 in neurodegenerative diseases

“…Interactions between IGF-1 and prostangladins are tissuedependant -in the brain, they have opposing effects. IGF-1 downregulates prostaglandins expression and therefore acts neuroprotective 28 . IL-1 and IL-6, activated by prostangladins and TNFα, were found to be particulary elevated in neurodegenerative conditions, where they also contributed in APP production.…”

“…The antagonistic relationship between IGF-1 and interleukins was also observed while measuring low levels of IGF-1 in the rat's brain and plasma after separate administration of IL-1 and IL-6. On the other hand, IGF-1 may act in a way that leads to a decrease in interleukin receptors expression and as a suppresor of cytokine signaling proteins 28 .…”