Research Article Open Access

Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome

Rodney Smith1, Lynda Thyer1, Emma Ward1, Elisabetta Meacci2, Jacopo J.V. Branca2, Gabriele Morucci2, Massimo Gulisano2, Marco Ruggiero2, Alessandra Pacini2, Ferdinando Paternostro2, Di Cesare Mannelli Lorenzo2, David J. Noakes3 and Stefania Pacini2
  • 1 Macro Innovations Ltd, United Kingdom
  • 2 University of Firenze, Italy
  • 3 Immuno Biotech Ltd; Channel Isles, Guernsey, Guernsey


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.

American Journal of Immunology
Volume 9 No. 4, 2013, 120-129


Submitted On: 29 October 2013 Published On: 6 November 2013

How to Cite: Smith, R., Thyer, L., Ward, E., Meacci, E., Branca, J. J., Morucci, G., Gulisano, M., Ruggiero, M., Pacini, A., Paternostro, F., Lorenzo, D. C. M., Noakes, D. J. & Pacini, S. (2013). Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome. American Journal of Immunology, 9(4), 120-129.

  • 4 Citations



  • Chronic Fatigue Syndrome
  • Immunotherapy
  • Vitamin D
  • Macrophage Activating Factor
  • GcMAF