[Experimental study on the therapeutic mechanism of high dose intravenous immunoglobulin in treatment of immune-mediated peripheral neuropathy].
OBJECTIVE
To explore the therapeutic basis of high dose intravenous immunoglobulin (IVIg) in treatment of peripheral neuropathy induced by Campylobacter jejuni lipopolysaccharide (CJ LPS).


METHODS
(1) IVIg (400 mg/kg x d) was given to the rats on the different days respectively during the immunization with CJ LPS. Histological study of sciatic nerve was performed on the 35 th day after immunization. The titer of anti-CJ LPS antibody in sera of immunized rats was measured by ELISA; IgG deposition was detected by immunohistochemistry and expression of TNF-alpha mRNA in the pathological nerves by in situ hybridization histochemistry. (2) When PBMCs were stimulated by CJ LPS in vitro, IVIg was added into culture medium at the doses of 1, 2.5, 5, and 10 mg/ml, respectively. Pathological examination of sciatic nerve was performed on the 7th day after perineural injection of the supernatants. Expression of TNF-alpha mRNA in PBMCs stimulated by CJ LPS in medium was detected by in situ hybridization histochemistry after adding IVIg.


RESULTS
(1) The rate of abnormal fibers appearance in IVIg group (1.0%) was much lower than that of the control group (15.0%) after immunization with CJ LPS, P < 0.01. The titer of antibody in control group was 9 times higher than that of IVIg group. There was no expression of immunoglobulin and TNF-alphamRNA in peripheral nerves in IVIg group, but high expression was found in control group in which no IVIg was injected. (2) The expression rates of TNF-alphamRNA on the PBMCs in IVIg group (1.0%) was much lower than that of control group (9.5%). (3) When the PBMCs of normal rats were stimulated by CJ LPS, the expression rates of TNF-alphamRNA in PBMCs of 5 mg/ml IVIg group (3.0%) or 10 mg/ml IVIg group (2.0%) were much lower than that of 1 mg/ml IVIg group (15.0%) or 2.5 mg/ml IVIg group (11.5%), P < 0.01. The rate of abnormal fibers appearance in 5 mg/ml IVIg group (9.8%) or 10 mg/ml IVIg group (8.5%) was much lower than that of 1 mg/ml IVIg group (50.0%), 2.5 mg/ml IVIg group (41.0%) or control group (50.8%) after the perineural injection with the supernatants, respectively, P < 0.01.


CONCLUSIONS
The therapeutic effect of high dose IVIg might be associated with inhibition of the humoral and cellular immunity simultaneously in peripheral neuropathy induced by CJ LPS.
Gao
Yu-xing
YX
Department of Neurology, Chongqing Children's Hospital, Chongqing University of Medical Sciences, Chongqing 400014, China.
Cai
Fang-cheng
FC
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha