Elevated transforming growth factor-beta concentration correlates with posttrauma immunosuppression.
OBJECTIVE
To determine whether trauma induces an increase in the concentration of circulating transforming growth factor-beta (TGF-beta), and whether there is a temporal correlation between plasma TGF-beta concentration and the development of posttrauma cellular immunosuppression.


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-beta levels, splenocyte phenotypes, mitogen-induced proliferation, interleukin-2 (IL-2) production, and IL-2 receptor (IL-2R) expression were determined at each time point.


RESULTS
Splenocyte proliferation increased on day 1 postinjury without corresponding change in IL-2 or plasma TGF-beta levels. Splenocyte proliferation and IL-2 production were suppressed on day 3 postinjury, while plasma TGF-beta 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-beta. The immune response is restored with normalization of TGF-beta concentration. These observations suggest that TGF-beta may contribute to posttrauma immunosuppression.
Meert
K L
KL
Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA.
Ofenstein
J P
JP
Genyea
C
C
Sarnaik
A P
AP
Kaplan
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D011043:Pokeweed Mitogens / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood*; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*
D007376:Interleukin-2; D011043:Pokeweed Mitogens; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D003208:Concanavalin A