Changes in Lymphocyte Activity after Thermal Injury

Abstract

A B S T R A C T The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect bum-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight ofthese patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness.Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to ongoing normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of bum patients.

Mechanisms of immune resolution

“…Work by a number of laboratories looking at mixed T-cell responses after thermal injury reported the existence of both the CD8 + (Tc, cytotoxic T-lymphocyte) T-cell population, which seemed to play the role of suppressor inducer cells (85)(86)(87)(88)(89), and the CD4 + (Th, T-helper lymphocyte) T-cell population, which seems to serve as suppressor effector cells. Similar observations have also been made looking at alternative models of tissue injury (90)(91)(92) and hemorrhage (93). However, despite these observations, few investigators have been able to isolate pure populations, which were either a functionally or phenotypically unique lineage of cells and were consistently immune suppressive.…”

Mechanisms of Neutropenia Involving Myeloid Maturation Arrest in Burn Sepsis

“…More importantly, G-CSF-stimulated proliferation in the burn plus infection group was similar to that seen in the absence of the colony-stimulating factor. These results, taken together with a shift toward the mitotic com- Figure 5. Northem blot analysis of bone marrow myeloperoxidase gene expression from control, burn, or bum plus infection mice.…”

Generation of suppressor cells in mice after surgical trauma.

“…Some investigators also report decreased levels of immunoglobulins and complement in these patients (5)(6)(7). Although the mechanisms by which severe injury induces immunosuppression are not yet clear, suppressor cells may be partially responsible as recently demonstrated by Miller and Baker (8).…”