Protective effect of an extract from Ascaris suum in experimental arthritis models

被引:50
作者
Castro Rocha, Francisco Airton [1 ]
Rocha Melo Leite, Ana Karine [1 ]
Lima Pompeu, Margarida Maria [2 ]
Cunha, Thiago Mattar [3 ]
Verri, Waldiceu A., Jr. [3 ]
Soares, Fernanda Macedo [4 ]
Castro, Rondinelle Ribeiro [1 ]
Cunha, Fernando Queiroz [3 ]
机构
[1] Univ Fed Ceara, Fac Med, Dept Internal Med, BR-60115281 Fortaleza, Ceara, Brazil
[2] Univ Fed Ceara, Fac Med, Dept Pathol, BR-60115281 Fortaleza, Ceara, Brazil
[3] Univ Sao Paulo, Dept Pharmacol, Fac Med, BR-14049 Sao Paulo, Brazil
[4] Inst Butantan, Dept Immunol, Sao Paulo, Brazil
关键词
D O I
10.1128/IAI.01085-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We investigated the effect of an extract from a helminth (Ascaris suum) in zymosan-induced arthritis (ZYA) or collagen-induced arthritis (CIA). Rats and mice, respectively, received 1 mg and 0.1 mg zymosan intra-articularly (i.a.). Test groups received an A. suum extract either per os (p.o.) or intraperitoneally (i.p.) 30 min prior to i.a. zymosan. Controls received saline. Hypernociception was measured using the articular incapacitation test. Cell influx, nitrite, and cytokine levels were assessed in joint exudates. The synovia and distal femoral extremities were used for histopathology. Cartilage damage was assessed through determining glycosaminoglycan (GAG) content. DBA/1J mice were subjected to CIA. The test group received A. suum extract i.p. 1 day after CIA became clinically detectable. Clinical severity and hypernociception were assessed daily. Neutrophil influx was determined using myeloperoxidase activity. The A. suum extract, either i.p. or p.o., significantly and dose-dependently inhibited cell influx and hypernociception in ZYA in addition to reducing GAG loss and ameliorating synovitis. The A. suum extract reduced i.a. levels of NO, interleukin-1 beta (IL-1 beta), and IL-10 but not tumor necrosis factor alpha (TNF-alpha) in rats subjected to ZYA while reducing i.a. IL-10, but not IL-1 beta or TNIT-alpha, levels in mice. Clinically, mice subjected to CIA treated with the A. suum extract had less severe arthritis. Hypernociception, myeloperoxidase activity, and synovitis severity were significantly reduced. These data show that a helminth extract given p.o. protects from arthritis severity in two classical arthritis models. This A. suum effect is species independent and functions orally and parenterally. The results show clinical and structural benefits when A. suum extract is given either prophylactically or therapeutically.
引用
收藏
页码:2736 / 2745
页数:10
相关论文
共 39 条
[11]   Nitric oxide-mediated chondrocyte cell death requires the generation of additional reactive oxygen species [J].
Del Carlo, M ;
Loeser, RF .
ARTHRITIS AND RHEUMATISM, 2002, 46 (02) :394-403
[12]   Opinion - A worm's eye view of the immune system: consequences for evolution of human autoimmune disease [J].
Dunne, DW ;
Cooke, A .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (05) :420-426
[13]   Helminths as governors of immune-mediated inflammation [J].
Elliott, David E. ;
Summers, Robert W. ;
Weinstock, Joel V. .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2007, 37 (05) :457-464
[14]  
Faquim-Mauro EL, 1998, CLIN EXP IMMUNOL, V114, P245
[15]   TLR2 modulates inflammation in zymosan-induced arthritis in mice [J].
Frasnelli, ME ;
Tarussio, D ;
Chobaz-Péclat, V ;
Busso, N ;
So, A .
ARTHRITIS RESEARCH & THERAPY, 2005, 7 (02) :R370-R379
[16]   Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006 [J].
Furst, D. E. ;
Breedveld, F. C. ;
Kalden, J. R. ;
Smolen, J. S. ;
Burmester, G. R. ;
Emery, P. ;
Keystone, E. C. ;
Schiff, M. H. ;
van Riel, P. L. C. M. ;
Weinblatt, M. E. ;
Weisman, M. H. .
ANNALS OF THE RHEUMATIC DISEASES, 2006, 65 :2-15
[17]  
GREENWOO.BM, 1968, LANCET, V2, P380
[18]   Genetics of autoimmune diseases - disorders of immune homeostasis [J].
Gregersen, Peter K. ;
Behrens, Timothy W. .
NATURE REVIEWS GENETICS, 2006, 7 (12) :917-928
[19]   Immune regulation by helminth parasites: Cellular and molecular mechanisms [J].
Maizels, RM ;
Yazdanbakhsh, M .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) :733-744
[20]   Parasite-mediated down-regulation of collagen-induced arthritis (CIA) in DA rats [J].
Mattsson, L ;
Larsson, P ;
Erlandsson-Harris, H ;
Klareskog, L ;
Harris, RA .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 122 (03) :477-483