Impact of burn injury on hepatic TGF-beta(1) expression and plasma TGF-beta(1) levels

Background: The liver plays a critical regulatory role in the acute inflamm atory response to injury, although the mechanisms of this regulation are no t well understood, transforming growth factor-beta(1) (TGF-beta(1)) is indu ced after burn injury and may contribute to an inhibitory or fatal effect o n hepatocytes. We investigated the association over time between plasma con centration of TGF-beta(1), expression of TGF-beta(1) m-RNA in liver tissue, and histologic analysis of liver apoptosis after burn injury. Methods: Male BALB/c mice were anesthetized and randomized to receive 0% (s ham), moderate (approximately 25%) (M), or large (approximately 50%) (L) bo dy surface area full-thickness contact burn, followed by resuscitation and analgesia. Animals were killed over a time course from 15 minutes to 24 hou rs after burn injury, and liver tissue and peripheral blood were collected. Plasma levels of TGF-beta(1) (nanograms per milliliter) were measured by e nzyme-linked immunosorbent assay, TGF-beta(1) m-RNA was extracted from live r and measured by reverse transcription-polymerase chain reaction. Histolog y of liver apoptosis was examined after fixation and staining with TdT-medi ated dUTP nick-end labeling (TUNEL) method. Results: The plasma concentration of TGF-beta(1) in burn group L was signif icantly increased at 4 hours after burn when compared with sham and hi burn groups. This rise in plasma TGF-beta(1) was preceded by an increase in hep atic TGF-beta(1) m-RNA expression at 30 minutes, 1, 2, and 4 hours after bu rn in the L group. Histologic analysis found greater hepatocyte death in th e L group than in the M group at 8 hours after burn. Conclusion: The levels of induced TGF-beta(1) and TGF-beta(1) m-RNA after L burn injury are higher and peak earlier than after M burn injury. Elevated TGF-beta(1) may be associated with cell death in hepatocytes, The TGF-beta (1) rise may be associated with hepatocyte injury and systemic response to massive burn.