Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Sep 27, 2022; 13(4): 72-82
Published online Sep 27, 2022. doi: 10.4331/wjbc.v13.i4.72
Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation
Malwina Rybicka-Ramos, Mirosław Markiewicz, Aleksandra Suszka-Świtek, Ryszard Wiaderkiewicz, Sylwia Mizia, Monika Dzierżak-Mietła, Krzysztof Białas
Malwina Rybicka-Ramos, Department of Hematology, Specialist Hospital No. 1 in Bytom, Bytom 41-902, Poland
Mirosław Markiewicz, Department of Hematology, University of Rzeszow, College of Medical Sciences, Institute of Medical Sciences, Rzeszów 35-315, Poland
Aleksandra Suszka-Świtek, Ryszard Wiaderkiewicz, Department of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice 40-752, Poland
Sylwia Mizia, Department of Population Health, Division of Epidemiology and Health Education, Wroclaw Medical University, Wrocław 51-618, Poland
Monika Dzierżak-Mietła, Department of Bone Marrow Transplantation and Hematooncology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice 44-102, Poland
Krzysztof Białas, Department of Hematology and Bone Marrow Transplantation, SPSK-M Hospital, Katowice 40-027, Poland
Author contributions: Rybicka-Ramos M contributed to conceptualization, methodology, investigation, data curation and analysis, original draft preparation, project administration, and fund acquisition; Markiewicz M contributed to methodology, investigation, manuscript review and editing, supervision, and fund acquisition; Dzierzak-Mietla M and Bialas K contributed to investigation; Suszka-Świtek A, Wiaderkiewicz R, and Mizia S contributed to data curation and analysis.
Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of the Medical University of Silesia in Katowice (No. KNW/0022/KB1/71/I/12).
Conflict-of-interest statement: All the authors declare no conflict of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Malwina Rybicka-Ramos, MD, PhD, Doctor, Department of Hematology, Specialist Hospital No. 1 in Bytom, 7 Zeromskiego Street, Bytom 41-902, Poland. malwina.rybicka@gmail.com
Received: March 8, 2022
Peer-review started: March 8, 2022
First decision: April 25, 2022
Revised: May 11, 2022
Accepted: September 21, 2022
Article in press: September 21, 2022
Published online: September 27, 2022
Processing time: 201 Days and 8.5 Hours
Abstract
BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs.

AIM

The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.

METHODS

We enrolled 62 patients, i.e., 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings (n = 12) or unrelated donors (n = 50) due to acute myeloid leukemia with myeloablative conditioning (n = 26; 42%) and with non-myeloablative conditioning (n = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA.

RESULTS

Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [n = 15 (24%)], group II consisted of patients with infections without acute GvHD [n = 17 (27%)], group III was comprised of patients with acute GvHD without infections [n = 9 (15%)], and group IV included patients with both acute GvHD and infections [n = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 (P = 0.014) and +30 (P = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I (P = 0.039) and IV (P = 0.017) compared to group II. The levels of IL-2 were mostly undetectable.

CONCLUSION

Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.

Keywords: Interleukin-2; Interferon-gamma; Cytokine profiles; Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Acute graft-versus-host disease

Core Tip: This paper presents the profiles of interleukin-2 and interferon-gamma levels depending on the occurrence of acute graft-versus-host disease and infection complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the cytokine levels were assessed in the early period after allo-HSCT (within the first 30 d after transplantation). Before, during, and after blood sampling for cytokine determination, cytokine-producing cells were not stimulated with mitogenic substances (lipopolysaccharide or phytohemagglutinin). Therefore, the obtained cytokine levels and their profiles may be regarded as those which reflect real values in patients who underwent allo-HSCT.