The evolution of an inflammatory response

Abstract

Background: The past 25 years have witnessed immense progress in our understanding of the systemic, tissue-specific, and cellular consequences of severe injury and infection. Despite such insights, considerable controversy remains regarding appropriate biologic and management interventions to prevent or ameliorate the associated adverse outcomes.

Methods: A review of several scientific developments arising from studies initiated at Cornell University Medical College during the tenure of Dr. G. Tom Shires. The implications of those and subsequent studies are discussed.

Results: An understanding of patient-specific variation and adaptability could direct individualized biologic and management interventions for severe injury and infection.

Conclusion: Despite more detailed appreciation of the molecular mechanisms of danger and pathogen recognition and response biology, we have much to learn about the complexity of severe injury and infection. There is a great need to extend our investigation of these mechanisms to experimental and stress-modified clinical scenarios.

FIG. 1.

Current and former members of the Laboratory of Surgical Metabolism at the New York Hospital-Cornell Medical Center with Dr. G. Tom Shires, circa 1991.

FIG. 2.

Representation of two-hit model of the inflammatory response. The systemic host phenotype as well as cellular responses respond to initial injury conditions as modified by individual patient features, such as age, sex, and associated illnesses or therapies. Over time, other influences, including management practices and acquired dampening of signal input or tissue responsiveness (“connectedness”), modify the inflammatory responses, including any resulting from secondary stressors. Tx = therapy.