Accession Number : ADA328889

Title :   Studies of Altered Response to Infection Induced by Severe Injury.

Descriptive Note : Final rept. 14 Apr 92-2 Jun 97

Corporate Author : MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER

Personal Author(s) : Miller-Graziano, Carol L.

PDF Url : ADA328889

Report Date : JUL 1997

Pagination or Media Count : 123

Abstract : Multiple organ dysfunction syndrome (MODS) is most frequent area of late eat in trauma patients and a particular problem for combat casualties where conflict conditions may not allow early evacuation to ICU units of extensive treatment. Consequently, delineating mechanisms for ameliorating posttrauma immunosuppression and overproduction of inflammatory cytokines is a major priority. Only the trauma patient subset with both MOe and T cell dysfunctions develop MODS. This patient subsets' MOe are producing large quantities of deregulated and aberrant TNF(sub alpha), indicated by increased TNF(sub alpha) mRNA stability, failure to shed heutralizing TNF, insensitivity to PGE(sub 2) and TGF(sub beta) downregulation, as well as predominant production of cell associated or mTNF(sub alpha). These aberrant post-injury MOe's ability to activate T cells is also decreased by loss of their IL-12 production and both helper 1 and helper 2 T lymphocyte responses are concomitantly depressed. Dysfunctional T cells fail to appropriately activate or regulate inflammatory MOe allowing exaggerated inflammatory monokines to cause MODS. Aberrant MOe function is detectable as an increase of MOe TNFR (failure to shed the TNFR) and surface expression of mTNF(sub alpha). Aberrant T lymphocyte activity is also rapidly indicated by depressed CD28 and CD3 expression and concomitant upregulation of CD11b expression. Rapid flow cytometric identification of altered MOe and T cell surface receptor/ligand combinations might serve as an easily implementable technique for screening combat casualties. This contract's data have implicated a combination of T lymphocyte and MOe dysfunctions as responsible for the development of MODS. Both a possible means of rapidly identifying combat casualties at risk of MODS and suggestions of future interventive therapy have been developed as a result of this contract

Descriptors :   *SIGNS AND SYMPTOMS, *WOUNDS AND INJURIES, *INFECTIOUS DISEASES, *DYSFUNCTION, WARFARE, RISK, CONTRACTS, PRODUCTION, CELLS, FAILURE, RESPONSE, CASUALTIES, CONFLICT, T LYMPHOCYTES, DEATH, INFLAMMATION, LYMPHOCYTES, ABNORMALITIES, IMMUNOSUPPRESSION, TRAUMA, ORGANS(ANATOMY).

Subject Categories : Medicine and Medical Research
      Stress Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE