Immunoaugmentation: A Contribution to Prophylaxis and Treatment of Sepsis?

Abstract

Trauma and the subsequent stress response have been associated with widely varied changes in host defense. A large body of information has been accumulated characterizing the various types of immune dysfunction following injury and suggests that major accidental, burn, or operative trauma causes substantial immunosuppression [1–4]. The deficit of immunocompetence together with an overwhelming nondiscriminant whole body inflammatory response explains the high susceptibility of the injured individual for developing sepsis with consecutive multiple organ dysfunction syndrome (MODS). We and others have demonstrated that the alterations of cell-mediated immunity (CMI) following trauma is mainly due to the disruption of intact monocyte (Mø)/T cell interaction [5, 6]. Within this phenomenon we see a shift of the cell ratio in the compartment of peripheral blood mononuclear cells (PBMCs) with a considerable increase of prostaglandin E₂ (PGE₂)-synthesizing Møs and a simultaneous decrease of functionally competent CD3+ and CD4+ lymphocytes. T cell dysfunction in states of profound mechanical stress is characterized by impaired synthesis of two crucial cytokines — interleukin-2 (IL-2) and γ-interferon (γ-IFN) [7, 8]. The inability to produce adequate amounts of IL-2 results in incomplete proliferative T cell responses to antigenic stimuli, while a lack of γ-IFN results in inefficient Mø antigen presentation. It has been demonstrated that both defects are keystones of suppressed CMI function following trauma with subsequent development of sepsis. The information derived from the dissection of down-regulatory mechanisms responsible for the development of injury-related immunoincompetence also provided incentive for the development of therapeutic regimens designed to prevent a major collapse of CMI.