Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs. (8th July 2015)

• Record Type: Journal Article
• Authors: Leoncini, Silvia; De Felice, Claudio; Signorini, Cinzia; Zollo, Gloria; Cortelazzo, Alessio; Durand, Thierry; Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef
• Other Names: El Jamali Amina Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2015(2015)
• Publication Date: 2015-07-08
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2015/421624
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene ( MECP2 ) or, more rarely, cyclin-dependent kinase-like 5 ( CDKL5 ). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2 - ( MECP2 -RTT) (n = 16 ) and CDKL5 -Rett syndrome ( CDKL5 -RTT) (n = 8 ), before and after ω -3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2 -RTT, a Th2-shifted balance was evidenced, whereas in CDKL5 -RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2 -RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5 -RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.