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Studies of Altered Response to Infection Induced by Severe Injury.
Midterm rept. 14 Apr 92-14 Oct 94,
MASSACHUSETTS UNIV MEDICAL CENTER WORCESTER
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The Systemic Inflammatory Response Syndrome SIRS that frequently occurs post-injury. is a major cause of post-trauma mortality and is characterized by both immunosuppression and cytokine aberrations. This research focuses on identifying the relative contributions of T cell and monocyte M0 aberrations to SIRS. In the first half of the contract, we have shown that MO TNFa production a major contributor to SIRS is aberrantly increased in trauma patients by 1 Failure to rapidly degrade TNFa mRNA leading to prolonged TNFa protein production 2. Insensitivity to normal downregulation by prostaglandin E2 and TGFa 3.Increased sensitivity of MO to TNFa induction by LTB4 4.Increased MO autocrine stimulation by TNFa due to stimulation through unshed TNFR 5.Decreased production of the TNFa immunoregulatory cytokine IL-1O by patients MO and T lymphocytes 6.Decreased T lymphocyte production of IF
APPROVED FOR PUBLIC RELEASE