---
title: "Postoperative Free Interleukin‑18 (IL‑18F) Correlates With Pain and Analgesic Use After Cholecyste"
id: "pubmed-42665372"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42665372"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42665372/"
doi: "10.21873/invivo.14435"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Postoperative Free Interleukin‑18 (IL‑18F) Correlates With Pain and Analgesic Use After Cholecyste
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42665372
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42665372/)
- **DOI:** [10.21873/invivo.14435](https://doi.org/10.21873%2Finvivo.14435)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This prospective randomized trial compared postoperative blood levels of **free interleukin‑18 (IL‑18F)**, IL‑18, and IL‑18 binding protein (**IL‑18BP**) with patient pain scores and analgesic consumption after cholecystectomy performed by minilaparotomy (MC) or laparoscopy (LC). - Blood measurements included IL‑18, IL‑18BP, IL‑18F and several other cytokine‑related markers; pain was assessed with the numerical rating scale (**NRS**) and analgesic use as number of analgesic doses (NAD). - **IL‑18F** strongly correlated with IL‑18 (r = 0.92, p < 0.001) and with Caspase‑1 (r = 0.64, p < 0.001), and showed weaker correlations with IL‑18BP (r = -0.260, p < 0.001), catalase (r = 0.13, p < 0.04), and nitrotyrosine (r = -0.16, p = 0.01). - IL‑18F blood levels increased postoperatively: the reported mean/median values at PRE and POP2 were 632 versus 739 (increase significant, p < 0.01). - Both **IL‑18F** and **IL‑18BP** showed statistically significant associations with patient‑reported pain (NRS: IL‑18F r = -0.16, p = 0.02; IL‑18BP r = 0.17, p = 0.02) and with analgesic dosing (NAD: IL‑18F r = -0.20, p = 0.016; IL‑18BP r = -0.16, p = 0.05) in the cholecystectomy cohort. - The authors conclude these are the first clinical data linking postoperative **IL‑18F** levels to NRS pain scores and analgesic requirements after cholecystectomy, suggesting roles for IL‑18F and IL‑18BP in the acute‑phase immune response to surgical trauma. - Source did not report some procedural details (sample size per arm, exact timing of POP2, analgesic regimens, or full cytokine panel numeric results) in the abstract; full text would be required for those specifics.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Surgery, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland; matti.eskelinen@kuh.fi. * 2 Department of Surgery, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland. * 3 Science Center, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland. * 4 Department of Ophthalmology, KUH and UEF, Kuopio, Finland. * PMID: **42665372** * DOI: [ 10.21873/invivo.14435 ](https://doi.org/10.21873/invivo.14435) Item in Clipboard Randomized Controlled Trial # Pain and Analgesic Doses _Versus_ Free Interleukin 18 (IL-18F) Blood Levels Following Surgery: A Prospective Randomized Study of Patients With Minilaparotomy Cholecystectomy _Versus_ Laparoscopic Cholecystectomy Matti Eskelinen et al. In Vivo. 2026 Sep-Oct. Show details Display options Display options Format Abstract PubMed PMID In Vivo Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22In+Vivo%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22In+Vivo%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42665372/) . 2026 Sep-Oct;40(5):2855-2863. doi: 10.21873/invivo.14435. ### Authors [Matti Eskelinen](https://pubmed.ncbi.nlm.nih.gov/?term=Eskelinen+M&cauthor_id=42665372)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-1 "Department of Surgery, Kuopio University Hospital \(KUH\) and School of Medicine, University of Eastern Finland \(UEF\), Kuopio, Finland; matti.eskelinen@kuh.fi."), [Viivi Kuosmanen](https://pubmed.ncbi.nlm.nih.gov/?term=Kuosmanen+V&cauthor_id=42665372)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-2 "Department of Surgery, Kuopio University Hospital \(KUH\) and School of Medicine, University of Eastern Finland \(UEF\), Kuopio, Finland."), [Tuomas Selander](https://pubmed.ncbi.nlm.nih.gov/?term=Selander+T&cauthor_id=42665372)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-3 "Science Center, Kuopio University Hospital \(KUH\) and School of Medicine, University of Eastern Finland \(UEF\), Kuopio, Finland."), [Kai Kaarniranta](https://pubmed.ncbi.nlm.nih.gov/?term=Kaarniranta+K&cauthor_id=42665372)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-4 "Department of Ophthalmology, KUH and UEF, Kuopio, Finland."), [Iina Saimanen](https://pubmed.ncbi.nlm.nih.gov/?term=Saimanen+I&cauthor_id=42665372)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-2 "Department of Surgery, Kuopio University Hospital \(KUH\) and School of Medicine, University of Eastern Finland \(UEF\), Kuopio, Finland."), [Maaret Eskelinen](https://pubmed.ncbi.nlm.nih.gov/?term=Eskelinen+M&cauthor_id=42665372)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42665372/#short-view-affiliation-2 "Department of Surgery, Kuopio University Hospital \(KUH\) and School of Medicine, University of Eastern Finland \(UEF\), Kuopio, Finland.") ### Affiliations * 1 Department of Surgery, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland; matti.eskelinen@kuh.fi. * 2 Department of Surgery, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland. * 3 Science Center, Kuopio University Hospital (KUH) and School of Medicine, University of Eastern Finland (UEF), Kuopio, Finland. * 4 Department of Ophthalmology, KUH and UEF, Kuopio, Finland. * PMID: **42665372** * DOI: [ 10.21873/invivo.14435 ](https://doi.org/10.21873/invivo.14435) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background/aim:** Cytokines (CYT) are regulators of the acute phase immune response (APR) to inflammation and trauma. The purpose of this work was to assess blood level correlations of various CYTs; interleukin-18 (IL-18), IL-18 binding protein (IL-18BP), free interleukin 18 (IL-18F) _versus_ numerical rating pain scale (NRS) and number of analgesic doses (NAD) following surgery in patients undergoing laparoscopic cholecystectomy (LC) or minilaparotomy cholecystectomy (MC). **Patients and methods:** Blood levels of IL-18, IL-18BP, IL-18F and five CYTs were determined and the NRS pain surveys were performed preoperatively (PRE) and postoperatively (POP). **Results:** The IL-18F blood levels correlated to IL-18 (_r_ =0.92, _p_ <0.001), IL-18BP (r=-0.260, _p_ <0.001), Caspase-1 (r=0.64, _p_ <0.001), catalase (r=0.13, _p_ <0.04), and nitrotyrosine (_r_ =-0.16, _p_ =0.01) blood levels. The IL-18F blood levels increased at POP and the increase between PRE and POP2 blood levels (632 _versus_ 739) was significant (_p_ <0.01). Moreover, the IL-18F and IL-18BP levels correlated significantly to NRS pain scales (r=-0.16, _p_ =0.02 and r=0.17, _p_ =0.02, respectively) and to the NAD levels (r=-0.20, _p_ =0.016 and r=-0.16, _p_ =0.05, respectively) in patients with cholecystectomy. **Conclusion:** This is the first report to demonstrate that postoperative IL-18F levels are significantly associated with NRS pain scores and the number of analgesic doses in patients undergoing cholecystectomy. These findings suggest that IL-18F and IL-18BP may contribute to the acute-phase immune response to surgical trauma and its relationship with postoperative pain and analgesic requirements. **Keywords:** IL-18 binding protein (IL-18BP); Interleukin-18 (IL-18); cytokines (CYTs); free interleukin 18 (IL-18F); surgery. Copyright © 2026, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Free Interleukin 18 (IL-18F) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer. ](https://pubmed.ncbi.nlm.nih.gov/39890196/) Eskelinen M, Selander T, Pulkkinen J, Kaarniranta K, Hämäläinen E, Eskelinen M.Eskelinen M, et al.Anticancer Res. 2025 Feb;45(2):667-675. doi: 10.21873/anticanres.17454.Anticancer Res. 2025.PMID: 39890196Clinical Trial. * [ A Possible Role of Interleukin-18 Binding Protein in Immune Regulation of Postoperative Pain: A Prospective Randomized Clinical Trial. ](https://pubmed.ncbi.nlm.nih.gov/37351998/) Eskelinen M, Saimanen I, Pulkkinen J, Selander T, Holopainen A, Hämäläinen E, Eskelinen M.Eskelinen M, et al.Anticancer Res. 2023 Jul;43(7):3113-3119. doi: 10.21873/anticanres.16483.Anticancer Res. 2023.PMID: 37351998Clinical Trial. * [ Blood Interleukin-18 (IL-18) and IL-18 Binding Protein (IL-18BP) Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer. ](https://pubmed.ncbi.nlm.nih.gov/38677734/) Eskelinen M, Selander T, Pulkkinen J, Hämäläinen E, Eskelinen M.Eskelinen M, et al.Anticancer Res. 2024 May;44(5):2039-2046. doi: 10.21873/anticanres.17007.Anticancer Res. 2024.PMID: 38677734Clinical Trial. * [ Brief Pain Inventory (BPI) Pain Survey _Versus_ Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer. ](https://pubmed.ncbi.nlm.nih.gov/39060040/) Eskelinen M, Selander T, Saimanen I, Pulkkinen J, Hämäläinen E, Eskelinen M.Eskelinen M, et al.Anticancer Res. 2024 Aug;44(8):3463-3471. doi: 10.21873/anticanres.17166.Anticancer Res. 2024.PMID: 39060040Clinical Trial. * [ Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis. ](https://pubmed.ncbi.nlm.nih.gov/38925829/) Eskelinen M, Selander T, Pulkkinen J, Holopainen A, Hämäläinen E, Eskelinen M.Eskelinen M, et al.Anticancer Res. 2024 Jul;44(7):2997-3003. doi: 10.21873/anticanres.17112.Anticancer Res. 2024.PMID: 38925829Clinical Trial. 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