Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome
Rodney Smith, Lynda Thyer, Emma Ward, Elisabetta Meacci, Jacopo J.V. Branca, Gabriele Morucci, Massimo Gulisano, Marco Ruggiero, Alessandra Pacini, Ferdinando Paternostro, Di Cesare Mannelli Lorenzo, David J. Noakes and Stefania Pacini
DOI : 10.3844/ajisp.2013.120.129
American Journal of Immunology
Volume 9, 2013
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of multifactorial aetiology characterized by immune system dysfunction, widespread inflammation, multisystemic neuropathology and persistent pain. Given the central role of the immune system in the pathogenesis of the syndrome, we studied the effects of a potent modulator of the immune system in in vitro and in vivo models that could help clarifying its role and indications in ME/CFS treatment. To this end, we studied the effects of vitamin D-binding protein-derived macrophage activating factor (also designated as Gc-Macrophage Activating Factor or (GcMAF)) on human neuronal cells (SH-SY5Y) and on the persistent pain induced by osteoarticular damage in rats. GcMAF at pM concentration increased neuronal cell viability and metabolism through increased mitochondrial enzyme activity. These effects were accompanied by cAMP formation and by morphological changes that were representative of neuronal differentiation. We hypothesize that these effects are to be ascribed to the interconnection between the GcMAF and Vitamin D Receptor (VDR) signalling pathways. The results presented here confirm at the experimental level the therapeutic effects of GcMAF in ME/CFS and elucidate the mechanisms of action through which GcMAF might be responsible for such therapeutic effects.
© 2013 Rodney Smith, Lynda Thyer, Emma Ward, Elisabetta Meacci, Jacopo J.V. Branca, Gabriele Morucci, Massimo Gulisano, Marco Ruggiero, Alessandra Pacini, Ferdinando Paternostro, Di Cesare Mannelli Lorenzo, David J. Noakes and Stefania Pacini. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.