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Cytokines, sepsis and the surgeon
J M Brown1, M A Grosso, A H Harken
1Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
Trauma and infection cause complex neuroendocrine responses. Afferent nervous stimuli, stimuli from the central nervous system, local wound factors and endocrine changes characterized by increases in stress hormones are some of these responses. Molecular biology has launched us into an age in which the categorization of these neuroendocrine changes will be broadened to include the profound effects of previously unidentified molecules. TNF and IL-1 are two protein hormones of the cytokine family. TNF causes hemorrhagic necrosis of solid tumors, mediates the lethal effects of endotoxemia and induces immune metabolic and intercellular changes. IL-1 is a mediator of inflammation and the acute phase response. The diversity of actions of TNF and IL-1 appear to be results of their multiple forms (alpha and beta) and their abilities to act both as membrane-associated and free proteins, to act locally (paracrine) as well as systemically, to act synergistically and to be involved in complex webs of self-promotion and amplification. On the basis of these diverse capabilities, they are prime candidates to be mediators of common surgical disease.
Insights
Trauma and infection trigger complex neuroendocrine responses. Novel molecules like tumor necrosis factor (TNF) and interleukin-1 (IL-1) are key mediators in surgical disease.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Immunology
Background:
- Trauma and infection induce complex neuroendocrine responses involving stress hormones.
- Molecular biology is revealing new mediators of these responses.
- Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytokines with diverse biological activities.
Purpose of the Study:
- To explore the role of previously unidentified molecules in neuroendocrine responses to trauma and infection.
- To investigate TNF and IL-1 as potential mediators of common surgical diseases.
Main Methods:
- Review of molecular biology findings on neuroendocrine responses.
- Analysis of the known functions and properties of TNF and IL-1.
Main Results:
- TNF mediates tumor necrosis, endotoxemia lethality, and immune/metabolic changes.
- IL-1 is a key mediator of inflammation and the acute phase response.
- TNF and IL-1 exhibit complex actions due to multiple forms, varied localization, synergistic effects, and self-amplification.
Conclusions:
- The diverse capabilities of TNF and IL-1 position them as significant mediators in common surgical diseases.
- Understanding these cytokine roles is crucial for advancing treatment strategies.