Whole Blood Reactivity to Viral and Bacterial Pathogens after Non-Emergent Cardiac Surgery during the Acute and Convalescence Periods Demonstrates a Distinctive Profile of Cytokines Production Compared to the Preoperative Baseline in Cohort of 108 Patients, Suggesting Immunological Reprogramming during the 28 Days Traditionally Recognized as the Post-Surgical Recovery Period

Krzysztof Laudanski; Da Liu; Lioudmila Karnatovskaia; Sanghavi Devang; Amal Mathew; Wilson Y Szeto

doi:10.3390/biomedicines12010028

Whole Blood Reactivity to Viral and Bacterial Pathogens after Non-Emergent Cardiac Surgery during the Acute and Convalescence Periods Demonstrates a Distinctive Profile of Cytokines Production Compared to the Preoperative Baseline in Cohort of 108 Patients, Suggesting Immunological Reprogramming during the 28 Days Traditionally Recognized as the Post-Surgical Recovery Period

Biomedicines. 2023 Dec 21;12(1):28. doi: 10.3390/biomedicines12010028.

Authors

Krzysztof Laudanski¹, Da Liu², Lioudmila Karnatovskaia³, Sanghavi Devang⁴, Amal Mathew⁵, Wilson Y Szeto⁶

Affiliations

¹ Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN 55905, USA.
² Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110055, China.
³ Division of Pulmonary and Critical Care, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
⁴ Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
⁵ School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
⁶ Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (t_baseline), followed by subsequent challenges during the acute phase (t_24h), convalescence (t_7d), and long-term recovery (t_3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils-IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells-M-CSF, IL-10). IL-2 and IL-10 were increased at t_7d, while TNFα was suppressed at t_24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t_3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.

Keywords: IL-10; IL-2; IL-6; M-CSF; TNFα; blood stimulation; cardiac surgery; immune system; inflammation; profiling; reprogramming.

Abstract

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