TREATMENT OF ADJUVANT ARTHRITIS IN RATS - VACCINATION POTENTIAL OF A SYNTHETIC NONAPEPTIDE FROM THE 65-KDA HEAT-SHOCK PROTEIN OF MYCOBACTERIA

被引:37
作者
YANG, XD
GASSER, J
RINIKER, B
FEIGE, U
机构
[1] Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd, Basle
关键词
D O I
10.1016/0896-8411(90)90003-B
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Adjuvant arthritis induced by mycobacteria in rats is a widely used model of chronic arthritis. A previously described nonapeptide (Thr-Phe-Gly-Leu-Gln-Leu-Glu-Leu-Thr, amino acid sequence 180-188) from the recombinant 65 kDa heat shock protein of Mycobacterium bovis BCG, which was found to contain a T-cell epitope recognized by both arthritogenic and protective T-cell clones in vitro, has been investigated for its vaccination and therapeutic potential in adjuvant arthritis in rats. The nonapeptide was found not to be arthritogenic, although the T cells from nonapeptide immunized rats cross-react in vitro with mycobacterial antigens. Intraperitoneal administration of 0.1 mg nonapeptide in oil at day -20 or days -2, -1 and 0, resulted in a marked reduction of incidence and severity of adjuvant arthritis. The disease process and severity were also influenced by therapeutic treatment with 0.1 mg nonapeptide injected intraperitoneally at days 7 to 10. Interestingly, subplantar or intravenous application of the nonapeptide had no influence on the disease process. Deletion of the N-terminal threonine led to complete loss of in vivo activity of the nonapeptide. © 1990.
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页码:11 / 23
页数:13
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