Elevated transforming growth factor-β concentration correlates with posttrauma immunosuppression

Objective: To determine whether trauma induces an increase in the concentration of circulating transforming growth factor-β (TGF-β), and whether there is a temporal correlation between plasma TGF-β concentration and the development of post-trauma cellular immunosuppression. Materials and Methods: Male Sprague-Dawley rats were anesthetized, subjected to bilateral femur fractures or sham injury, and killed 1, 3, or 5 days later. Plasma TGF- β levels, splenocyte phenotypes, mitogen-induced proliferation, interleukin- 2 (IL-2) production, and IL-2 receptor (IL-2R) expression were determined at each time point. Measurements and Main Results: Splenocyte proliferation increased on day 1 postinjury without corresponding change in IL-2 or plasma TGF-β levels. Splenocyte proliferation and IL-2 production were suppressed on day 3 postinjury, while plasma TGF-β levels peaked. No differences were observed between trauma and control groups on day 5. Splenocyte phenotypes and IL-2R expression were similar in injured and control rats at all times. Conclusions: Suppression of lymphocyte proliferation and IL-2 production after trauma occurs concomitantly with a rise in plasma TGF-β. The immune response is restored with normalization of TGF-β concentration. These observations suggest that TGF-β may contribute to posttrauma immunosuppression.