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
Feb 28, 1992·Science·M IsobeA Ihara
Jan 1, 1992·Transplantation·S M KramsJ P Roberts
Feb 1, 1992·Transplantation·S F BollingH Lin
Feb 1, 1992·Transplantation·O M MartinezN L Ascher
Jan 1, 1991·Transplantation·D K ImagawaR W Busuttil
Aug 1, 1990·Transplantation·D K ImagawaR W Busuttil
Dec 1, 1989·The Journal of Experimental Medicine·D F FiorentinoT R Mosmann
Jan 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·T CollinsJ S Pober
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·M P BevilacquaM A Gimbrone
Oct 1, 1987·The Journal of Experimental Medicine·G E RangesM A Palladino
Feb 1, 1969·The Journal of Thoracic and Cardiovascular Surgery·K Ono, E S Lindsey
Apr 15, 1983·Cellular Immunology·B KleinB Serrou
Mar 31, 1995·The Journal of Biological Chemistry·J RaingeaudR J Davis
Jan 1, 1994·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·J M Cavaillon
Aug 5, 1994·Science·J HanR J Ulevitch
Dec 22, 1994·Nature·J C LeeP R Young
Oct 24, 1996·European Journal of Pharmacology·N YamamotoM Okuhara
May 30, 1997·European Journal of Pharmacology·N YamamotoM Okuhara
Jun 20, 1998·The Journal of Biological Chemistry·S MatsudaE Nishida
Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J KobayashiY Morishita
Dec 30, 1998·Transplantation·H Y LanR Bucala
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