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Infection and Immunity, June 2008, p. 2736-2745, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01085-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Protective Effect of an Extract from Ascaris suum in Experimental Arthritis Models{triangledown}

Francisco Airton Castro Rocha,1* Ana Karine Rocha Melo Leite,1 Margarida Maria Lima Pompeu,2 Thiago Mattar Cunha,3 Waldiceu A. Verri Jr.,3 Fernanda Macedo Soares,4 Rondinelle Ribeiro Castro,1 and Fernando Queiroz Cunha3

Departments of Internal Medicine,1 Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil,2 Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil,3 Department of Immunology, Instituto Butantan, São Paulo, Brazil4

Received 6 August 2007/ Returned for modification 27 September 2007/ Accepted 25 March 2008

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-1β (IL-1β), 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-1β or TNF-{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.

* Corresponding author. Mailing address: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza 60115281, Brazil. Phone and fax: 55 85 32446215. E-mail: arocha{at}ufc.br

{triangledown} Published ahead of print on 14 April 2008.

Editor: J. F. Urban, Jr.

Infection and Immunity, June 2008, p. 2736-2745, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01085-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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