The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression.
Haemorrhage in the absence of trauma is reported to induce a profound depression in cell-mediated immunity. Recent studies have drawn attention to the cytokine transforming growth factor-beta (TGF-beta) that, while important in wound healing, also has marked immunosuppressive effects. The aim of this study was to determine whether: (1) haemorrhage induces an increase in circulating TGF-beta and if this is associated with the loss of host immunoresponsiveness; and (2) administration of monoclonal antibody (mAb) to TGF-beta following haemorrhage ablates these changes. To determine this, C3H/HeN mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 1 hr. This required removing approximately 50% of the circulating blood volume. Following this period of hypotension, the mice were adequately resuscitated. Blood samples obtained at 24 and 72 hr, but not at 2 hr, following haemorrhage showed a significant elevation in plasma TGF-beta levels when compared to shams. At 24 hr, the increase of TGF-beta in the plasma was associated with decreases in both concanavalin A (Con A)-induced splenocyte proliferation and splenic macrophage antigen presentation. Treating animals with neutralizing antibody (animals received 200 micrograms mAb against bovine TGF-beta 1,2,3/mouse intraarterially) not only reduced the levels of TGF-beta in the blood at 24 hr, but also restored splenocyte functions, such as Con A-induced proliferation, interleukin-2 (IL-2) release, and the capacity of splenic macrophages to present antigen. However, elevated levels of prostaglandin E2 (PGE2) seen in plasma during haemorrhage were only partially depressed by the antibody treatment. These results indicate that the release of TGF-beta contributes to the protracted (> or = 24 hr) suppression of cell-mediated immunity following haemorrhage.
Ayala
A
A
Dept. of Surgery, Michigan State University, East Lansing 48824.
Meldrum
D R
DR
Perrin
M M
MM
Chaudry
I H
IH
D000818:Animals; D015232:Dinoprostone / Q000276:immunology; D006470:Hemorrhage / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*
D016212:Transforming Growth Factor beta; D015232:Dinoprostone