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РЖ ВИНИТИ 34 (BI39) 96.02-04К1.643

Role of TNF'альфа' in the induction of antigen induced arthritis in the rabbit and the anti-arthritis effect of species specific TNF'альфа' neutralising monoclonal antibodies [Text] / Jo Lewthwaite [et al.] // Ann. Rheum. Diseases. - 1995. - Vol. 54, N 5. - P366-374 . - ISSN 0003-4967
Перевод заглавия: Роль фактора некроза опухоли-'альфа' (ФНО-'альфа') в возникновении вызываемого антигеном артрита у кролика и антиревматоидное действие видоспецифического ФНО-'альфа' нейтрализующих моноклональных антител
Аннотация: Monoclonal antibodies to rabbit TNA'альфа' were developed in rats and were used to detect TNF'альфа' in synovial fluid by enzyme linked immunosorbent assay and to localise it in tissue sections of synovium and cartilage from rabbits up to 21 days after induction of AIA. An antibody which neutralised TNF'альфа' activity in vitro was injected into rabbits to block TNF'альфа' action in vivo in AIA. Joint swelling, leucocyte infiltration into synovium and proteoglycan loss from cartilage were measured and compared with a control group, which were injected with sterile saline. Monoclonal antibodies to purified rabbit TNF'альфа' were prepared in rats and two were selected which were able to neutralise rabbit TNF'альфа' in a cytotoxicity bioassay. TNF'альфа' was detected in significant concentrations (21.7 (SE 0.5) pg/ml) in the arthritic joint fluid of rabbits with AIA only at one day after induction and it was then also sparsely localised in cells of ghe synovium, but from day 3 onwards it was localised more strongly in the deep zone of articular cartilage. Injection of anti-TNF monoclonal antibody R6 over three days into rabbits with AIA reduced joint swelling and leucocyte infiltration into joint fluid and decreased the expression of CD11b and CD18 on cells in the joint fluid. However, there was no singificant reduction in the loss of proteoglycan from articular cartilage, although the joint fluid at three days contained a lower glycosaminoglycan content. The antibody R6 gave most effect at a dose of 0.6 mg/kg and there was no increase in its effectiveness at a fiveflod greater dose (3.0 mg/kg). Treatment over 10 days gave a more complete suppression of joint swelling, but did not result in any less proteoglycan loss from cartilage. Treatment for five days with a 16 day follow up gave a significant reduction in swelling for several days beyond the treatment, but the swelling then slowly returned, untial by day 21 there was no significant difference in joint swelling and there was also no recovery of cartilage proteoglycan content. A rabbit anti-rat immunoglobulin response was detected at 21 days, which may have liminted the long term effectiveness of the antibody. Великобритания, Kennedy Inst. Rheumatol., London. Библ. 35

ГРНТИ	34.43.57

ВИНИТИ 341.43.57.29
Рубрики: ФАКТОР НЕКРОЗА ОПУХОЛИ АЛЬФА
ПАТОГЕННАЯ РОЛЬ
ЭКСПЕРИМЕНТАЛЬНЫЙ АРТРИТ
МОНОКЛОНАЛЬНЫЕ АНТИТЕЛА
АНТИРЕВМАТОИДНАЯ АКТИВНОСТЬ
КРОЛИКИ

Доп.точки доступа:
Lewthwaite, Jo; Blake, Simon; Hardingham, Timothy; Foulkes, RolandStephens Sue; Chaplin, Lesley; Emtage, Spencer; Catterall, Cath; Short, Steven; Nesbitt, Andrew; Allen, Rodger; Bodmer, Mark; Brown, Derek; Andrew, David; Henderson, Henderson

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