The two immune phenotypes of microg

The two immune phenotypes of microglial cells during brain inflammation. A detrimental/pro-inflammatory immune cell M1 phenotype is acquired upon classical activation of resting microglia by either LPS or INF-gamma, while IL-4, IL-10 or IL-13 typically induce an anti-inflammatory M2 phenotype representing an alternative, apparently beneficial, activation state more related to a fine tuning of inflammation, scavenging of debris, promotion of angiogenesis, tissue remodeling and repair. M1 cells release pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-1 beta and free radicals, that contribute to amplifying the neuroinflammatory response. Pro-inflammatory cytokines exert cytotoxic effects on oligodendrocytes and neurons leading to demyelination and axonal damage. M2 cells release neurotrophic factors such as GDNF, BDNF, bFGF, IGF-1, TGF-beta, HGF that provide trophic support to neurons in the injured area, in part by potentiating the recruitment, proliferation and differentiation of oligodendrocyte precursor cells. Autoregulatory processes, including phagocytosis of cellular debris and apoptotic cells, can down-regulate the activated M1 phenotype by a negative feed-back mechanism (20). This may result in the shift of M1 towards the M2 phenotype. Presently, it is not known whether the opposite (i.e., the shift from a detrimental M2 to a beneficial M1 phenotype) is possible, nor are known the endogenous signals involved in this shift. Purinergic signalling is involved in these changes at various stages (see text). A similar activation state had been previously reported for blood-borne macrophages