Theophylline improves early allograft function in rat kidney transplantation.
Several previous studies have demonstrated a beneficial effect of the adenosine receptor (AdoR) antagonist theophylline in different forms of acute renal failure in laboratory animals and in humans. Therefore, we wanted to test whether theophylline can also improve impaired allograft function following ischemia reperfusion injury in experimental kidney transplantation (KT). Orthotopic transplantation of the left kidney was performed from Fisher 344 into Lewis rats. All transplanted rats received daily cyclosporine (5 mg/kg). The effect of theophylline treatment (10 mg/kg) on graft function was compared with appropriate controls on day 5 after KT by assessment of glomerular filtration rate (GFR) (inulin clearance). On day 5, GFR of allografts in control rats was 0.23 +/- 0.05 ml/min/g kidney weight (n = 10) compared with 0.50 +/- 0.09 ml/min/g in rats receiving theophylline (n = 9, p < 0.01), representing a 2-fold increase in GFR. Renal AdoR A(1) mRNA content was significantly increased in both KT groups compared with their respective control groups, whereas mRNA of AdoR A(2a), A(2b), and A(3) were found to be unchanged. Theophylline did not affect significantly interstitial infiltration of the graft by monocytes/macrophages and T-cells. Likewise, serum cytokines [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-alpha] and erythropoietin plasma levels were not different among the allograft groups. The present study demonstrates that theophylline remarkably improved early renal allograft function in rats undergoing KT without influencing cytokine serum patterns or tissue inflammation. Since theophylline is a commonly used medication in humans, clinical studies in patients undergoing KT are warranted.
Grenz
Almut
A
Institute of Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tuebingen, Germany.
Baier
Detlef
D
Petroktistis
Fotios
F
Wehrmann
Manfred
M
Köhle
Christoph
C
Schenk
Martin
M
Sessler
Michael
M
Gleiter
Christoph H
CH
Fandrich
Fred
F
Osswald
Hartmut
H
D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007672:Kidney Cortex / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D004921:Erythropoietin; D013806:Theophylline