Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat.
Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.
Smith
T
T
Miriam Marks Department of Neurochemistry, Institute of Neurology, London, United Kingdom.
Hewson
A K
AK
Kingsley
C I
CI
Leonard
J P
JP
Cuzner
M L
ML
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000473:pathology*; D005260:Female; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D012008:Recurrence; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology
D011994:Recombinant Proteins; D018664:Interleukin-12; D019001:Nitric Oxide Synthase