Anti-intercellular adhesion molecule-1 (ICAM-1) antibody treatment prevents central and peripheral nervous system disease in autoimmune-prone mice.
Abnormal neurological functioning similar to that seen in systemic lupus erythematosus (SLE) patients is detectable in an SLE-prone murine strain (MRL/lpr) by 8-10 weeks and is severe by 18 weeks of age. The purpose of this study was to evaluate the effectiveness of murine antiintercellular adhesion molecule-1 (ICAM-1) in suppressing neurological disease in MRL/lpr mice. Beginning at 6 weeks of age, five MRL/lpr mice received 5 weekly intraperitoneal injections of anti-ICAM-1-containing culture supernatant in phosphate-buffered saline (PBS) whereas four animals were treated with non-anti-ICAM-1 containing supernatant in PBS. A decline in neurological functioning began in control mice by 10 weeks, but anti-ICAM-1 treated mice remained normal throughout the study. All control mice had vasculitic skin lesions by 14 weeks of age whereas none of the anti-ICAM-1 treated mice ever developed skin lesions. Nerve conduction studies performed on all mice prior to sacrifice showed sciatic compound motor action potentials of anti-ICAM-1 treated mice that were of higher amplitude and shorter latency than those of controls. Inflammation in the sciatic nerve was more common in control mice. Brain histology revealed a similar degree of choroid plexus inflammation in both groups. Our study demonstrated that anti-ICAM-1 was effective in suppressing neurological abnormalities in MRL/lpr mice and may potentially be useful therapy in human SLE.
Brey
R L
RL
Department of Neurology, University of Texas Health Science Center at San Antonio 78284-7883, USA.
Amato
A A
AA
Kagan-Hallet
K
K
Rhine
C B
CB
Stallworth
C L
CL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001927:Brain Diseases / Q000517:prevention & control*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000628:therapy*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1