The Significance and Challenges of Monocyte Impairment: For the Ill Patient and the Surgeon.

Abstract

Trauma, major elective surgery, and overt sepsis can lead to a cascade of immunological change. A subset of these patients will have a degree of immune suppression that leads to hyporesponsive innate defenses, increasing the risk of infective co-morbidity and death. This article is an overview of monocyte impairment in the high-risk surgical patient. Specifically, our primary focus is on observations made pertaining to monocyte function and pathophysiological mechanisms underpinning this impairment. Clinical factors influencing monocyte function are also discussed. A Pubmed search was conducted to review aspects of monocyte impairment in the surgical patient. Search terms included "monocyte impairment," "immunoparalysis," and "endotoxin tolerance" cross-referenced against terms including "trauma," "major surgery," and "sepsis." Findings revealed a broad variety of monocyte defects reported in surgical patients. They ranged from altered cytokine responses, particularly ex vivo TNF-α production, to impaired antigen presentation such as depressed HLA-DR expression. The latter is the most commonly described marker of secondary infection and death. Studies of underlying mechanisms have commonly utilized a model of endotoxin tolerance with in vitro monocytes, revealing a complex array of dysregulated pathways. For our purposes, endotoxin tolerance and monocyte impairment are sufficiently similar entities to permit further study as a single subject. In the high risk patient, microRNAs (also referred to as miRNA or miR) are emerging as potential biomarkers that may modify such pathways. Creation of a reliable impaired human monocyte model could be important to all such considerations. Impairment of monocyte function continues to be predictive of nosocomial infection, multi-organ failure, and death in some surgical patients. However, the optimal marker that could identify a patient as high risk early enough, and whether it might guide potential therapy, still is yet to be proven.