PMID: 11343986May 10, 2001Paper

Prolonged survival of rat cardiac allograft with proinflammatory cytokine inhibitor

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
I SanoH Ayabe

Abstract

Proinflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1), play important roles in acute allograft rejection. FR167653 is an inhibitor of these cytokines that acts through inhibition of the mitogen-activated protein kinase p38 pathway. We examined the effect of FR167653 on allograft rejection. We used Brown-Norway and Lewis rats as donors and recipients, respectively. We performed heterotopic cardiac transplantation. The control group consisted of untreated rats. In the experimental groups, recipients were intraperitoneally injected with FR167653 just after operation, followed by daily injection of the drug from Day 1 to 10. We divided 20 rats into 5 groups, which received varying doses of FR167653, ranging from 75 to 300 mg/kg/day. In the control group, the mean graft survival was 6.8 +/- 0.3 days. FR167653 at 150 mg/kg/day significantly prolonged the survival period (up to 12.1 +/- 1.5 days, p = 0.002). Histologically, FR167653 markedly suppressed cellular infiltration on Day 5 post-transplantation. The serum level of TNF-alpha in the control group was persistently elevated from 9.3 +/- 3.9 pg/ml to 11.3 +/- 3.8 pg/ml, whereas FR167653 significantly suppressed the level to <1.4 +/- 1.4 pg/m...Continue Reading

References

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Citations

Jul 30, 2004·Molecular and Cellular Biology·Kozo Ohkusu-TsukadaKatsuyuki Yui
Oct 7, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Irina A IonovaGalen M Pieper
Aug 18, 2004·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Horst FingerhuthThomas H W Stadlbauer
Feb 21, 2003·Progress in Transplantation : Official Publication, North American Transplant Coordinators Organization ... [et Al.]·Xiaopeng ZhangYushan Bai
Dec 2, 2005·Toxicology Letters·Waldemar WagnerJarosław Dastych
Dec 10, 2019·Clinical Transplantation·Aws AlmuflehSharon Chih

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