Burns 27 (2001) 739–746 Treatment with cerium nitrate bathing modulate systemic leukocyte activation following burn injury: an experimental study in rat cremaster muscle flap Muhittin Eski *, M. Deveci, B. C ¸ eliko ¨z, M. Nisanci, M. Tu ¨ regu ¨n Department of Plastic and Reconstructie Surgery, Burn Center, Gu ¨lhane Military Medical Academy, 06018 Etlik, Ankara, Turkey Accepted 2 March 2001 Abstract It is suggested that burn toxin known as lipid protein complex (LPC) stimulates phagocytic cells that cause the release of a variety of inflammatory mediators which induce the activation of leukocytes. It is reported that cerium nitrate (CN) might fix LPC in eschar tissue and prevent LPC from entering the circulation. In this study, we tested the hypothesis that prevention or modulation of LPC initiated cell activation by fixing LPC in eschar tissue with CN treatment, would reduce the number of activated leukocytes, which is an important indicator of inflammation, in rat cremaster muscle flap model. Twenty-eight animals were studied in four groups — group I (control), only cremaster muscle flap was dissected; group II (burn injury), burn injury was performed and flap was dissected; group III (saline); and group IV (CN), following burn injury rats treated with saline and CN, respectively, and than flaps were dissected. Blood vessels were observed in vivo under an intravital microscopy system and the number of rolling, sticking, and transmigrating leukocytes were measured in each group. Burn injury significantly increased the number of activated leukocytes (P 0.001). We observed that CN treatment significantly reduced the number of activated leukocytes following burn injury (P 0.001). In conclusion, we demonstrated that CN treatment significantly decreased the activation of leukocytes, which plays an important role in systemic inflammation. Decreased leukocyte activation is interpreted as prevention or modulation of systemic inflammatory response following burn injury. © 2001 Elsevier Science Ltd and ISBI. All rights reserved. Keywords: Burn; Cerium nitrate; Leukocyte activation www.elsevier.com/locate/burns 1. Introduction Despite the execution of modern and recent burn treatment modalities, the prevention of mortality and morbidity of burn injury is still an important problem. It has been recently reported that burn injury related mortality is due to systemic inflammatory response syndrome (SIRS) rather than uncontrolled infection and related complications [1,2]. Thermal injury induces phagocytic cell activation that causes the release of a variety of cytokines, prostaglandins and other inflammatory mediators [3,30]. The cytokines especially TNF- and IL-1 induce systemic leukocyte and endothelial cell activation fol- lowing burn injury [3 – 7]. This activation results in leukocyte – endothelial cell interaction, which consists of three sequential and distinct steps — rolling, tight adhesion, and transmigration [3,8]. The interaction be- tween leukocyte and endothelial cell plays a major role in the pathogenesis of inflammation, tissue repair, or self-tissue damage [8]. Although the appropriate activa- tion of leukocyte and endothelial cell can act benefi- cially to provide for enhanced host resistance and commence wound healing, any further injury, or septic insult as seen in burn injury, results in a hugely am- plified inflammatory response [30]. Therefore, inappro- priate, or unlimited activation may contribute to development of SIRS and multiple organ dysfunction syndrome (MODS) following the burn injury [3,9]. Leukocytes make a one-way journey from the bone marrow to tissues where they carry out their effector * Tel.: +90-312-3174180; fax: +90-312-3045412. E-mail address: muhittineski@hotmail.com (M. Eski). 0305-4179/01/$20.00 © 2001 Elsevier Science Ltd and ISBI. All rights reserved. PII:S0305-4179(01)00038-9