The role of macrophages in experimental autoimmune neuritis induced by a P2-specific T-cell line.
A P2-specific T-cell line with a helper/inducer phenotype (W3/25+) mediates experimental autoimmune neuritis in the Lewis rat after adoptive transfer to naive recipients. Moderately severe disease was induced in these experiments by the injection of 1 x 10(7) T cells. Motor and mixed afferent nerve conduction, F responses, H reflexes, and lumbar somatosensory evoked potentials were monitored, and morphological alterations were scored semiquantitatively at the end of the experiments. The role of macrophages and macrophage-derived inflammatory mediators in the effector phase of the disease was investigated by administering different inhibitors of macrophage metabolism, including silica, dexamethasone, and a variety of cyclooxygenase and lipoxygenase blockers. Silica and dexamethasone suppressed the clinical, electrophysiological, and morphological manifestations of the disease almost completely, indicating that macrophages are essential for the generation of inflammatory lesions. The inhibitors of arachidonic acid conversion failed to mitigate the severity of the disease. This is in contrast to observations in actively induced experimental autoimmune neuritis in which eicosanoid biosynthesis seems to play a decisive role in the pathogenesis of the disease.
Heininger
K
K
Department of Neurology, University of Düsseldorf, West Germany.
Schäfer
B
B
Hartung
H P
HP
Fierz
W
W
Linington
C
C
Toyka
K V
KV
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D005260:Female; D008264:Macrophages / Q000502:physiology*; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*