Investigation on the mechanism of exacerbation of myasthenia gravis by aminoglycoside antibiotics in mouse model.
To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruends adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23%, 58.82% and 63.16% respectively, which were significantly higher than those of MG group and NS group (40.00%, 40.00%, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.
Liu
Changqin
C
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hu
Fang
F
D000583:Amikacin / Q000009:adverse effects; D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D005260:Female; D005839:Gentamicins / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D011950:Receptors, Cholinergic; D000583:Amikacin