Systemic complement depletion reduces inflammation and demyelination in adoptive transfer experimental allergic neuritis

Abstract

The effect of systemic complement depletion by cobra venom factor (CVF) was evaluated in adoptive transfer experimental allergic neuritis (AT-EAN). Spleen cells of rats immunized with a neuritogenic peptide SP26 were injected into naive rats. On days 3 and 6 after cell transfer AT-EAN rats were treated with CVF or saline intraperitoneally. AT-EAN rats treated with CVF had significantly lower scores for histological inflammation (0.25 ± 0.25 vs 1.9 ± 0.4, mean ± SEM, P < 0.03) and demyelination (0.13 ± 0.13 vs 1.6 ± 1.4, P < 0.02) than saline-treated AT-EAN rats. Immunocytochemistry of lumbosacral nerve roots showed significantly less ED1-positive macrophages (0.5 ± 0.3 vs 1.6 ± 0.6, P < 0.04) and CD11bc-positive (expressing complement receptor 3 or CR3) inflammatory cells (0.6 ± 0.4 vs 1.7 ± 0.5, P < 0.03). Our data suggest that complement plays a crucial role in inflammatory demyelination since systemic complement depletion significantly reduces recruitment of macrophages into the nerve and subsequent macrophage-mediated demyelination.