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Review
. 2023 Feb 2:10:1086003.
doi: 10.3389/fvets.2023.1086003. eCollection 2023.

The impact of stress and anesthesia on animal models of infectious disease

Rachel Layton  1 , Daniel Layton  1 , David Beggs  2 , Andrew Fisher  2 , Peter Mansell  2 , Kelly J Stanger  1
Affiliations
Review

The impact of stress and anesthesia on animal models of infectious disease

Rachel Layton et al. Front Vet Sci. .

Abstract

Stress and general anesthesia have an impact on the functional response of the organism due to the detrimental effects on cardiovascular, immunological, and metabolic function, which could limit the organism's response to an infectious event. Animal studies have formed an essential step in understanding and mitigating infectious diseases, as the complexities of physiology and immunity cannot yet be replicated in vivo. Using animals in research continues to come under increasing societal scrutiny, and it is therefore crucial that the welfare of animals used in disease research is optimized to meet both societal expectations and improve scientific outcomes. Everyday management and procedures in animal studies are known to cause stress, which can not only cause poorer welfare outcomes, but also introduces variables in disease studies. Whilst general anesthesia is necessary at times to reduce stress and enhance animal welfare in disease research, evidence of physiological and immunological disruption caused by general anesthesia is increasing. To better understand and quantify the effects of stress and anesthesia on disease study and welfare outcomes, utilizing the most appropriate animal monitoring strategies is imperative. This article aims to analyze recent scientific evidence about the impact of stress and anesthesia as uncontrolled variables, as well as reviewing monitoring strategies and technologies in animal models during infectious diseases.

Keywords: animal immunity; animal models of disease; animal monitoring; impacts of anesthesia; impacts of stress; infectious disease research; laboratory animal welfare; surgical stress.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Hypothalamic-pituitary axis (HPA) activation, sympathetic nervous system activation, and compensatory mechanisms in response to stress. Sympathetic nervous system activation occurs as the primary response to stress, followed by HPA axis activation where the stressor is prolonged or chronic. A negative feedback loop leads to compensatory mechanisms via the HPA axis in response to threats to homeostasis.
Figure 2
Figure 2
Effects of acute and chronic stress on glucocorticoid and immune responses in laboratory animals. Common routine stressors of laboratory animals include manual handling, blood collection, and noise. When these stressors are acute, enhanced glucocorticoid production via stimulation of the sympathetic nervous system and HPA axis result in an enhanced immune response. When stressors are chronic, the development of glucocorticoid resistance leads to immunosuppression. This primarily occurs via a decreased and altered leukocyte production in addition to a reduced production of anti-inflammatory cytokines via a negative feedback loop.
Figure 3
Figure 3
Clinical and subclinical effects of anesthesia lead directly and indirectly to immunosuppression. Clinical effects are those that can be detected by monitoring and assessment, whilst sub-clinical effects are not readily detected. In both instances anesthetic effects either directly result in immunosuppression or result in further physiological effects that in turn result in immunomodulation, most commonly immunosuppression via a reduced inflammatory response. The incidence and significance of effects vary depending on the anesthetic agents used, time spent under anesthesia, species being anesthetized and degree of supportive care provided.
Figure 4
Figure 4
Data collected from Web of Science. Search refined by categories of Veterinary Sciences, Infectious Diseases, Agriculture multidisciplinary, Zoology. Search conducted of title, abstract, and key words using these terms per category: *Machine learning animal disease, algorithm animal disease. ∧Subjective assessment animal disease, clinical scoring animal disease, grimace score animal disease, clinical assessment animal disease. ~Heart rate animal disease, rectal temperature animal disease, blood pressure animal disease, respiration. ∨Sensors animal disease, wearable animal disease. ¨Video monitoring animal disease, infrared monitoring animal disease, motion detection monitoring animal disease.
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Grants and funding

Funding support was provided through an Australian Government Research Training Program Scholarship.

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