Effects of pentoxyfylline on mesenteric lymph node T-cells in A rat model of thermal injury

• Published in: Shock (Augusta, Ga.) Ga.), 2003-12, Vol.20 (6), p.517-520
• Main Authors: KOTADIA, Bharat K, RAVINDRANATH, Thyyar M, CHOUDHRY, Mashkoor A, HAQUE, Farah, AI-GHOUL, Walid, SAYEED, Mohammed M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Burns; Calcium - metabolism; Cell Division; Concanavalin A - pharmacology; Hematologic Agents - therapeutic use; Immunoblotting; Interleukin-2 - biosynthesis; Interleukin-2 - metabolism; Lymph Nodes - pathology; Lymphocyte Activation; Male; Medical sciences; Pentoxifylline - therapeutic use; Pharmacology. Drug treatments; Phosphorylation; Precipitin Tests; Rats; Rats, Sprague-Dawley; Signal Transduction; Skin, nail, hair, dermoskeleton; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/01.shk.0000098103.41147.54

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.