TY - JOUR
T1 - Immunomodulation of experimental autoimmune myasthenia gravis with linomide
AU - Karussis, D. M.
AU - Lehmann, D.
AU - Brenner, T.
AU - Wirguin, I.
AU - Mizrachi-Koll, R.
AU - Sicsic, C.
AU - Abramsky, O.
N1 - Funding Information:
The authors are indebted to Dr. A. Mahler for her editorial assistance. This research was supported in part by a grant from the Chief Scientist of the Israel Ministl3, of Health, and in part by the Isobel and Martin Slomovitz Grant and the Hilda Katz Blaustein Neurological Fund.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Linomide, a synthetic immunomodulator, increases natural killer (NK) activity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the autoimmune manifestations of lupus-like disease in MRL/lpr and the clinical and pathological signs of acute and chronic-relapsing experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined the effect of linomide (100 mg/kg/day; administered in drinking water) on rabbits and rats with experimental autoimmune myasthenia gravis (EAMG). Following immunization with Torpedo acetylcholine receptor (AChR), all control rabbits developed clinical signs of severe weakness and exhibited a decrement of muscle action potential upon repetitive stimulation. In contrast, mild signs of weakness appeared in only two of five linomide-treated rabbits, with EMG borderline positive in one of them. Booster immunization with Torpedo AChR induced severe relapse and death in two EAMG control rabbits, whereas the two linomide-treated animals remained free of myasthenic symptoms. The serum level of antibodies against both Torpedo and rat AChR were markedly suppressed in the linomide-treated animals. Similar inhibition of clinical signs of EAMG was observed in the EAMG rat model. Furthermore, the in vitro proliferative response of lymp node cells to Torpedo AChR and the purified protein derivative of Mycobacterium tuberculosis was significantly lower in the linomide-treated EAMG rats than in the controls. Linomide may constitute a new immunomodulating agent for the treatment of myasthenia gravis.
AB - Linomide, a synthetic immunomodulator, increases natural killer (NK) activity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the autoimmune manifestations of lupus-like disease in MRL/lpr and the clinical and pathological signs of acute and chronic-relapsing experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined the effect of linomide (100 mg/kg/day; administered in drinking water) on rabbits and rats with experimental autoimmune myasthenia gravis (EAMG). Following immunization with Torpedo acetylcholine receptor (AChR), all control rabbits developed clinical signs of severe weakness and exhibited a decrement of muscle action potential upon repetitive stimulation. In contrast, mild signs of weakness appeared in only two of five linomide-treated rabbits, with EMG borderline positive in one of them. Booster immunization with Torpedo AChR induced severe relapse and death in two EAMG control rabbits, whereas the two linomide-treated animals remained free of myasthenic symptoms. The serum level of antibodies against both Torpedo and rat AChR were markedly suppressed in the linomide-treated animals. Similar inhibition of clinical signs of EAMG was observed in the EAMG rat model. Furthermore, the in vitro proliferative response of lymp node cells to Torpedo AChR and the purified protein derivative of Mycobacterium tuberculosis was significantly lower in the linomide-treated EAMG rats than in the controls. Linomide may constitute a new immunomodulating agent for the treatment of myasthenia gravis.
KW - Experimental autoimmune myasthenia gravis
KW - Immunomodulation
KW - Linomide
KW - Myasthenia
UR - http://www.scopus.com/inward/record.url?scp=0028559752&partnerID=8YFLogxK
U2 - 10.1016/0165-5728(94)90009-4
DO - 10.1016/0165-5728(94)90009-4
M3 - Article
C2 - 7829669
AN - SCOPUS:0028559752
SN - 0165-5728
VL - 55
SP - 187
EP - 193
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 2
ER -
