Effects of pentoxyfylline on mesenteric lymph node T-cells in a rat model of thermal injury.
Cutaneous burn injury-induced T lymphocyte suppression is a well-known phenomenon. In this study, we evaluated the effect of treatment of burn rats with pentoxifylline (PTX) on the burn-induced suppression of T lymphocytes. Anesthetized rats were subjected to 30% total body surface area burn by exposing skin to 95 degrees C water for 10 s. T lymphocytes were isolated from sham and burn rats with or without PTX treatment (120 mg/kg, ip). T cell proliferation and interleukin (IL)-2 production in response to T cell mitogen concanavalin A was measured using 3 H-thymidine uptake and enzyme-linked immunosorbent assay, respectively. P59 fyn autophosphorylation and its kinase activity was determined using in vitro kinase assay. In addition, T lymphocyte Ca2+ signaling was assessed using Ca2+ imaging technique. Two days after injury, there was a significant decrease in mesenteric lymph node T cell proliferation and IL-2 production in burn injured rats compared with those obtained from sham-injured rats. This decrease in T cell proliferation and IL-2 production in burn-injured rats was accompanied by a significant suppression in both P59 autophophorylation and kinase activity as well as Ca2+ signaling. Treatment of burn-injured rats with PTX produced a near complete recovery of T cell proliferation and IL-2 production. Furthermore, PTX treatment also prevented the burn-mediated suppression in P59fyn and kinase activity as well as restored Ca2+ signaling similar to those observed in sham injured rats. These findings altogether suggested that PTX treatment attenuate T cell suppression in burn-injured rats and that the effects of PTX are mediated via modulating P59 fyn and Ca2+ signaling.
Kotadia
Bharat K
BK
Department of Surgery, Trauma/Critical Care Research Laboratories, Ronald McDonald Children's Hospital, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Ravindranath
Thyyar M
TM
Choudhry
Mashkoor A
MA
Haque
Farah
F
Al-Ghoul
Walid
W
Sayeed
Mohammed M
MM
D000818:Animals; D002056:Burns; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D006401:Hematologic Agents / Q000627:therapeutic use*; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D010431:Pentoxifylline / Q000627:therapeutic use*; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D006401:Hematologic Agents; D007376:Interleukin-2; D003208:Concanavalin A; D010431:Pentoxifylline; D002118:Calcium