Differences in toll-like receptor ligand-induced cytokine concentrations before and after solid organ transplantation: A prospective, observational cohort study in a clinical setting

Dina Leth Møller, Søren Schwartz Sørensen, Michael Perch, Finn Gustafsson, Annemette Hald, Andreas Delhbæk Knudsen, Ranya Abdulovski, Nicoline Stender Arentoft, Jens Lundgren, Allan Rasmussen, Sisse Rye Ostrowski, Susanne Dam Nielsen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Reliable methods to assess immune function after solid organ transplantation (SOT) are needed to guide dosing of immunosuppression. We hypothesized that toll-like receptor ligand-induced cytokine concentrations would decrease post-transplantation due to the use of immunosuppressive medication. Furthermore, we hypothesized that induced cytokine concentrations pre-transplantation would be higher in recipients with episodes of acute rejection post-transplantation due to underlying immunological dispositions. We aimed to investigate toll-like receptor ligand-induced cytokine concentrations by TruCulture©, a standardized immunoassay, in SOT recipients before and 3 months after SOT and explored associations with methylprednisolone-treated acute rejections. We conducted a prospective, observational cohort study including 123 participants (67 liver, 32 kidney and 24 lung transplant recipients). Whole blood was stimulated for 22 h with: (A) Lipopolysaccharide (LPS), (B) Resiquimod, (C) Polyinosinic:polycytidylic acid (Poly I:C) and (D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α and IFN-γ) were measured by Luminex. 30 participants developed methylprednisolone-treated acute rejection at a median of 9 days (IQR 5–17) post-SOT. We found that all induced cytokine concentrations decreased post-SOT except from LPS-induced and Poly I:C-induced IL-10. The induced cytokine concentration pre-transplantation did not differ in recipients with or without acute rejection. In conclusion, the induced cytokine concentrations decreased for all stimuli post-SOT, except the anti-inflammatory cytokine IL-10. Importantly, recipients developing early acute rejection did not differ in induced cytokine concentrations pre-SOT. Thus, the use of a standardized assay in SOT is feasible in a clinical setting and may provide important information on the immune function post-SOT.
OriginalsprogEngelsk
Artikelnummere13337
TidsskriftScandinavian Journal of Immunology
Vol/bind99
Udgave nummer2
Antal sider13
ISSN0300-9475
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
This work was supported by the Novo Nordic Foundation, the Independent Research Fund (FSS), the Danish National Research Foundation (DNRF) grant no. 126, and the Research Foundation of Rigshospitalet. The funding sources were not involved in any part of the study design, data collection, data analysis, and interpretation of the data or the writing of this manuscript.

Publisher Copyright:
© 2023 The Scandinavian Foundation for Immunology.

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