Effects of autoantigen and dexamethasone treatment on expression of endothelial-monocyte activating polypeptide II and allograft-inflammatory factor-1 by activated macrophages and microglial cells in lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis.

Endothelial-monocyte activating polypeptide II (EMAP II) and allograft-inflammatory factor-1 (AIF-1) are two proteins produced by activated monocytes and microglial cells. We now report expression of these factors during experimental therapy of rat neuroautoimmune diseases. Comparative analysis of two therapeutic strategies, treatment with high doses of recombinant autoantigens or with dexamethasone, revealed unexpected differences. High doses of autoantigen were most effective in experimental autoimmune encephalomyelitis and neuritis (EAE and EAN), but less effective in experimental autoimmune uveitis (EAU). Low and high doses of dexamethasone treatment greatly reduced the severity of EAE, EAN and EAU at day 11, but a relapse was observed between days 21 and 26. Only rather limited expression of EMAP II and AIF-1 is seen in the normal central nervous system (CNS). This constitutive expression is not abolished by dexamethasone treatment. In inflammatory autoimmune lesions of the rat CNS, prominent AIF-1 and EMAP II staining was seen with macrophages and monocytes. In particular, parenchymal microglial cells were now activated to express AIF-1 and EMAP II. In accordance with prevention of neurological signs, histological observations revealed that accumulation of activated monocytes expressing EMAP II and AIF-1 in the CNS or peripheral nervous system and the massive expression of these factors by parenchymal microglial cells is inhibited by high doses of autoantigen. Dexamethasone prevented or abolished local expression of EMAP II and AIF-1 at days 10-16. However, an acute and severe relapse occurred in encephalomyelitis between days 20-26. In these cases, a smoldering expression of EMAP II and AIF-1 persisting long after cessation of neurological signs was observed. Thus, expression of EMAP II and AIF-1 by infiltrating activated macrophages is a marker of disease activity and expression of these factors could be used to demonstrate 'silent' lesions in the CNS and prolonged microglial cell activation. Apparently, AIF-1 and EMAP II immunoreactivity are tools to stage activation of monocytes and microglial cells in inflammatory lesions.