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Review
. 2025 Dec 26;17(12):e100101.
doi: 10.7759/cureus.100101. eCollection 2025 Dec.

Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes

Kirtish Acharya  1 , Deepak Kumar Rout  2 , Nilaykumar A Kapadia  3 , Yash Satish Caroicar  4 , Naresh Babu Karunakaran  5 , Punit Patel  6 , Harsiddh Thaker  7
Affiliations
Review

Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes

Kirtish Acharya et al. Cureus. .

Abstract

Surgical intervention triggers a complex physiological cascade, also known as the surgical stress response, which entails well-coordinated immunological, metabolic, and neuroendocrine processes. This systematic review summarizes the existing evidence from 11 studies published between 2015 and 2025, investigating the underlying mechanisms, regulatory interactions, and clinical implications of this multifactorial response. Central stress pathway activation triggers immediate hormonal increase, stabilizing circulation and energy reserves, but chronic endocrine stimulation has the potential to increase metabolic and immune imbalances and results in a delayed recovery. The ensuing immune dynamics display an initial inflammatory phase followed by transient suppression, collectively influencing tissue repair and infection susceptibility. Parallel metabolic adaptations enhance energy production but often induce insulin resistance and protein catabolism, contributing to postoperative fatigue and functional decline. These interdependent mechanisms form a unified neuroendocrine-immune-metabolic network that can shift from adaptive to maladaptive under persistent stress. New evidence indicates that biomarkers such as cortisol, IL-6, glucose, and albumin serve as predictors of postoperative complications, including infection, impaired wound healing, and increased morbidity. Various perioperative interventions, such as the Enhanced Recovery After Surgery programs, immunonutrition, and metabolic administration, exhibit the possibility of maximizing such responses. The review combines both mechanistic and clinical perspectives to promote precision-based perioperative tactics to enhance surgical and recovery outcomes.

Keywords: biomarkers; immunometabolism; neuroendocrine regulation; perioperative medicine; surgical stress response.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. PRISMA flow diagram.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2. Cytokine dynamics post surgery.
The figure was created by the authors. TNF-α: tumor necrosis factor-alpha; IL: interleukin.
See this image and copyright information in PMC

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