The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis.

Abstract The selective toxicity of silica quartz dust for macrophages was used to assess the role of these cells in experimental allergic encephalomyelitis. A single dose of 200 mg silica dust given to Lewis rats 8 days post-sensitization caused a delay in onset of clinical signs and a reduction in the severity of the disease. Animals given a 2nd injection of silica on day 11 showed a further delay in onset of symptoms and a further reduction in the clinical incidence of disease such that 80% of the animals were not paralyzed and remained asymptomatic for at least 4 wk after the injection of the silica. To test for the role of the macrophage as an effector cell in EAE, some animals were not challenged with silica until after the onset of early clinical signs. Intraperitoneal injection of 200 mg caused a remarkable arrest in the progression of clinical and pathologic signs. The conclusion that i.p. injection of silica dust protects against EAE by the depletion of macrophages, and not by a direct effect on the function of the sensitized lymphocyte, is supported by the following results; 1) i.p. challenge with thioglycolate broth failed to stimulate an adherent cell population in silica-treated animals; 2) the lysosomal stabilizing agent poly-2-vinylpyridine N-oxide, which has been shown to protect macrophages against the toxic effect of silica, partially abrogated the protection afforded by silica; and 3) functionally reactive lymphocytes could be demonstrated in the lymph nodes by proliferative responses to the sensitizing antigens BP and PPD, and in the spleen by successful passive transfer of disease to normal animals after in vitro stimulation with Con A. These results strongly support the conclusion that cells of the monocyte-macrophage series function as effector cells in the clinical and pathologic expression of an autoimmune inflammatory demyelinating disease.