Beta-endorphin prevents collagen induced arthritis by neuroimmuno-regulation pathway.
OBJECTIVE
To observe the effects and mechanisms of beta-endorphin (beta-END) preventing collagen induced arthritis (CIA) by neuroimmuno-regulating pathway.


METHODS
Female wistar (Ws) rats were used in this study. CIA was induced by Native bovine type II collagen emulsified with complete Freund's adjuvant (CFA). Beta-END was administered i.p. to CIA rats every other day from the 14th day (secondary immunization) to the 35th day after primary immunization. Clinical assessments were performed by two independent, blinded examiners every other day. Pathological and radiological observations were taken on the 35th day after the primary immunization. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), regulated upon activation, normal T-cell expressed and secreted (RANTES), inducible NO syntheses (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA expression of synovium tissues of CIA rats was estimated by quantitative RT-PCR. The frequency of spleen Th1 and Th2 cells were assessed by fluorescence activated cell sorter (FACS) assay.


RESULTS
Clinical manifestation of rats with CIA were significantly abrogated or ameliorated by treatment with beta-END. Beta-END treatment in vivo could down-regulate mRNA expression of several pro-inflammatory cytokines, chemokines and MMPs in CIA synovial, and polarize Th1/Th2 balance to Th2.


CONCLUSIONS
Beta-END alleviates CIA through both depressing Th1 responses and down-regulating proinflammatory and other rheumatic factors, suggesting beta-END is a promising anti-inflammatory and anti-rheumatic agent in treating CIA.
Yin
Hongen
H
Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, 1 Shuaifuyuan,Wangfujing, Beijing, 100730 PR China.
Yu
Mengxue
M
Cheng
Hong
H
Zhang
Fengchun
F
Gao
Yang
Y
Lin
Jiayou
J
Han
Bing
B
Zhu
Liping
L
D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000276:immunology* / Q000517:prevention & control*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D003094:Collagen; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D018655:Lymphocyte Count; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D001615:beta-Endorphin / Q000276:immunology*
D018946:Chemokine CCL5; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001615:beta-Endorphin; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9