Severe trauma or thermal injury induce the appearance of serum factors that suppress cell-mediated immunity, as measured by lymphocyte proliferative response. This phenomenon has been shown to correlate with a higher incidence of infectious complications after accidental and operative trauma. We have found recently that moderately severe hemorrhage alone in """"""""untraumatized"""""""" and unanesthetized rats was sufficient to bring about the appearance in the blood of such an immunosuppressive factor. It is the objective of the proposed research to (1) define the conditions necessary for suppressive factor production by examining serum suppressive activity after hemorrhage of graded severity; (2) isolate a sufficient amount of this suppressive factor, purify it to electrophoretic homogenity, and determine its molecular weight; (3) ascertain the mechanism(s) which underlie the immunosuppressive action of the serum factor(s) by determining its effect on the generation and proliferation of helper and suppressor T cells, on interleukin-2 production by stimulated lymphocytes as well as determining possible counter actions by exogeneous interleukin-2. The results generated from the proposed experiments should provide information which may permit the development of methods to better identify and correct the suppression of lymphocyte proliferative capacity which exists after trauma and hemorrhage, leading to decreased rates of infection, morbidity and mortality after trauma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
5R23AI022944-02
Application #
3445773
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Abraham, E (1989) Host defense abnormalities after hemorrhage, trauma, and burns. Crit Care Med 17:934-9
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Abraham, E; Freitas, A A (1989) Hemorrhage in mice induces alterations in immunoglobulin-secreting B cells. Crit Care Med 17:1015-9
Abraham, E; Freitas, A A (1989) Hemorrhage produces abnormalities in lymphocyte function and lymphokine generation. J Immunol 142:899-906
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Abraham, E; Richmond, N J; Chang, Y H (1988) Effects of hemorrhage on interleukin-1 production. Circ Shock 25:33-40
Abraham, E; Tanaka, T; Chang, Y H (1988) Effects of hemorrhagic serum on interleukin-2 generation and utilization. Crit Care Med 16:307-11
Abraham, E; Regan, R F; Chang, Y H (1986) Lack of effect of exogenous recombinant interleukin-2 on trauma-induced abnormalities in lymphocyte proliferation. Crit Care Med 14:847-51