Immunologic alterations and the pathogenesis of organ failure in the ICU

Rapid and marked alterations of innate and adaptive immunity typify the host response to systemic infection and acute inflammatory states. Immune dysfunction contributes to the development of organ failure in most patients with critical illness. The molecular mechanisms by which microbial pathogens and tissue injury activate myeloid cells and prime cellular and humoral immunity are increasingly understood. An early and effective immune response to microbial invasion is essential to mount an effective antimicrobial response. However, unchecked and nonresolving inflammation can induce diffuse vasodilation, increased capillary permeability, microvascular damage, coagulation activation, and organ dysfunction. Control of the inflammatory response to limit tissue damage, yet retain the antimicrobial responses in critically ill patients with severe infection, has been sought for decades. Anti-inflammatory approaches might be beneficial in some patients but detrimental in others. It is now clear that a state of sepsis-induced immune suppression can follow the immune activation phase of sepsis. In carefully selected patients, a better therapeutic strategy might be to provide immunoadjuvants to reconstitute immune function in intensive care unit (ICU) patients. Proresolving agents are also in development to terminate acute inflammatory reactions without immune suppression. This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness.