Alterations in transcriptional regulation of proinflammatory and immunoregulatory cytokine expression by hemorrhage, injury, and critical illness.

Transcriptional factors which bind to the promoter regions of genes play an important role in regulating gene expression. The transcription of immunoregulatory and proinflammatory cytokines as well as other proteins known to be important in producing organ system injury after trauma, blood loss, or sepsis is controlled both by the activation of transcriptional regulatory factors and by the interactions of these transcriptional factors with each other, resulting in augmentation or suppression of gene transcription. Most of the transcriptional factors which appear to play a role in modulating immune response in the setting of critical illness can be activated through several different pathways, often involving intracellular redox state and cytokine or endotoxin interaction with membrane receptors. In the severely injured patient, many of these activating mechanisms appear to be operative. Modulation of gene transcription, particularly in those organ systems (e.g., the lungs) which are most vulnerable to inflammatory injury, may be an important therapeutic target in critically ill patients.