Severely injured patients develop host defense defects which can be directly correlated to an increased incidence of septic complications. In particular, development of augmented regulatory cells, both inhibitory monocytes (inh M0phi) and suppressor T lymphocyte (Ts), have been linked to post-trauma immunincompetence. The hypothesis under investigation is that inimical alterations in vital M-phi-T cell interactions play a pivotal role in the post-trauma development of excessive regulatory cells and immune depression. Consequently, monitoring certain crucial patient M-phi functions should allow characterization of patients' host defense status. The proposed experiments will simultaneously assess different trauma patient M-phi functions and correlate alterations in these M-phi functions to both modulation in T-cell activity and incidence of clinical complications. The first experimental set examines post-trauma alterations in M-phi production of mediators as exemplified by (1) Plasminogen Activator production, (2) Procoagulant activity generation, (3) Leukocyte Pyrogen/Interleukin 1(Il-l) synthesis by examining both Il-l general activation of T-cells and activation of specific T-cell subssets (i.e. Ts vs Th), (4) Production of Complement components and (5) Synthesis of Prostaglandin E-2s(PGE2)h. Any identified alteration in M-phi mediator production will be compared to changes in M-phi immune interactions as detected by the second set of experiments. The second experimental set analyzes changes in M-phi-T cell interactions, such as (1) Decreased M-phi antigen presenting capacity, (2) Increased M-phi activation of Ts, (3) Increased M-phi inhibititory activity for Th, and (4) Increased susceptivility of M-phi populations to suppression, either Ts or PGE2 mediated. If M-phi immune interactions are altered, M-phi ability to respond to stimulation will be affected. The third experimental set evaluates post-trauma variation in the response capacity of trauma patients' M-phi to known non-specific M-phi activators including Fc fragments, muramyl dipeptide(MDP) and peptidoglycan. Once inimical alterations in M-phi immune capacity are identified, they will be related to a physical change in M-phi subset surface receptors. Finally, any post-trauma alterations in important M-phi surface receptors and/or antigens, which are crucial in certain M-phi functions, will be delineated so that an aberrant M-phi can be identified solely on the basis of its stable marker phenotype. This will allow immediate detection of immunoincompetent patients and simplify monitoring of patients receiving prophylactic immunotherapy.
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