EFFECTS OF GC-MACROPHAGE ACTIVATING FACTOR IN HUMAN NEURONS; IMPLICATIONS FOR TREATMENT OF CHRONIC FATIGUE SYNDROME

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of multifactoria l aetiology characterized by immune system dysfunction, widespread inflammation, multisystemic neuropathology and persistent pain. Given the centr al role of the immune system in the pathogenesis of the syndrome, we studied the effects of a potent modula tor of the immune system in in vitro and in vivo mo dels 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 macrop hage activating factor (also designated as GcMacrophage 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 incr eased 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 e ffects of GcMAF in ME/CFS and elucidate the mechanisms of action through which GcMAF might be responsible for such therapeutic effects.