Cecal ligation and puncture peritonitis model shows decreased nicotinic acetylcholine receptor numbers in rat muscle - Immunopathologic mechanisms?

Background: Although systemic inflammation is believed to cause upregulatio n of nicotinic acetylcholine receptors (nAchRs) in muscle, chronic infectio ns such as Chagas' disease occasionally are complicated by myasthenia gravi s, The authors investigated how a nonlethal cecal ligation and puncture (CL P) peritonitis model in rats could affect muscle nAchR. Methods: On day 1, 4, 7, 14, or 21 after WP or sham operation, nAchR bindin g was assayed in the anterior tibial muscle and diaphragm using [I-125]alph a-bungarotoxin. The presence or absence of weakness, in vivo dose-response relationships for d-tubocurarine, and serum anti-nAchR antibody titers were assayed in separate experiments, Results: Systemic inflammation was most severe during the first 4 to 5 days . Numbers of nAchRs were decreased in anterior tibial muscle on days 7, 14, and 21 after CLP, and in the diaphragm on days 7 and 14 (P < 0.01), Both 5 0% and 90% blocking doses of d-tubocurarine) were lower in CLP rats than in sham-operated rats on days 7, 14, and 21 (P < .05). Weakness was overt in approximately half of CLP rats at these times. Serum anti-nAchR antibody (0 .7-1.4 nM) was detectable beginning on day 4 and continuing throughout the 21-day observation period in 58-67% of CLP rats, Conclusions: During the recovery phase of injury, nonlethal CLP peritonitis resulted Ln downregulation of nAchR. However, further study is needed to d etermine the role of anti-nAchR antibodies in the development of decreased receptor numbers and impaired neuromuscular function.