Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1396800
This article is part of the Research Topic Organ crosstalk and other responses to an activated immune system in trauma and disease View all 3 articles

Femoral nailing associated with bone marrow emboli in pigs induced a specific increase in blood IL-6 and broad inflammatory responses in the heart and lungs

Provisionally accepted
Steinar Kristiansen Steinar Kristiansen 1,2*Benjamin S. Storm Benjamin S. Storm 1,2,3Åse Emblem Åse Emblem 1Renathe Grønli Renathe Grønli 1Kristin Pettersen Kristin Pettersen 1Jonas Hilmo Jonas Hilmo 1,2Anders H. Jarmund Anders H. Jarmund 4Martin Leth-Olsen Martin Leth-Olsen 4,5Siri Ann Nyrnes Siri Ann Nyrnes 4,5Bent A. Nilsen Bent A. Nilsen 1,3Erik W. Nielsen Erik W. Nielsen 1,2,3Tom E. Mollnes Tom E. Mollnes 1,6
  • 1 Nordland Hospital, Bodø, Nordland, Norway
  • 2 UiT The Arctic University of Norway, Tromsø, Troms, Norway
  • 3 Nord University, Bodø, Nordland, Norway
  • 4 NTNU, Trondheim, Sør-Trøndelag, Norway
  • 5 St Olav's University Hospital, Trondheim, Sør-Trøndelag, Norway
  • 6 University of Oslo, Oslo, Norway

The final, formatted version of the article will be published soon.

    Background. Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear.We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses.Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow.Methods. Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro. Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1β, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays.Results. After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004).No plasma differences in the rest of the inflammatory markers were noted across groups.However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1β and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1β compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro, incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03).A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source.

    Keywords: Bone marrow embolization, Fat embolism syndrome, Inflammation, orthopedic surgery, complement, Cytokines

    Received: 06 Mar 2024; Accepted: 02 Jul 2024.

    Copyright: © 2024 Kristiansen, Storm, Emblem, Grønli, Pettersen, Hilmo, Jarmund, Leth-Olsen, Nyrnes, Nilsen, Nielsen and Mollnes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Steinar Kristiansen, Nordland Hospital, Bodø, 8092, Nordland, Norway

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.