Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Supportive Care in Cancer
Published in: Supportive Care in Cancer 6/2015

01-06-2015 | Original Article

The relationship between oral mucositis and levels of pro-inflammatory cytokines in serum and in gingival crevicular fluid in allogeneic stem cell recipients

Authors: Karin Garming Legert, Georgios Tsilingaridis, Mats Remberger, Olle Ringdèn, Anders Heimdahl, Tülay Yucel-Lindberg, Göran Dahllöf

Published in: Supportive Care in Cancer | Issue 6/2015

Login to get access

Abstract

Purpose

Oral mucositis (OM) is a severe side effect of conditioning for allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the present study was to investigate the relationship between oral mucositis and the levels of pro-inflammatory cytokines—both in serum and in gingival crevicular fluid (GCF), in relation to different conditioning regimens.

Methods

We analyzed the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-7, as well as anti-inflammatory cytokine IL-10 in gingival crevicular fluid (GCF) and in serum from 43 HSCT patients. Twenty-five received reduced intensity conditioning (RIC) and 18 received myeloablative conditioning (MAC). Cytokine levels were determined in GCF and serum before the start of conditioning, and 1 week and 1 month after HSCT. All patients experienced OM with a median score of 2.1 and median peak on day 11.

Results

There was a significant correlation between OM and MAC (p = 0.035). There were no significant differences in GCF volume at the three time points examined. The levels of IL-6 in GCF increased 1 week after transplantation and then returned to baseline (p < 0.001). The levels of IL-10 in GCF decreased after HSCT (p < 0.001) and remained unchanged. The levels of IL-6 in serum significantly (p < 0.001) increased 1 week after HSCT and decreased to baseline levels after 1 month. The levels of IL-10 in serum significantly (p = 0.02) increased 1 month after HSCT.

Conclusion

No correlations between cytokine levels in gingival crevicular fluid and oral mucositis were observed. There was a correlation between severity of OM score and increase in IL-6 in serum. No correlations between cytokine levels in gingival crevicular fluid and in serum were observed.
Literature
1.
Sonis ST, Elting LS, Keefe D et al (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025CrossRefPubMed
2.
Vagliano L, Feraut C, Gobetto G et al (2011) Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT—results of a multicentre study. Bone Marrow Transplant 46:727–732CrossRefPubMed
3.
Al-Dasooqi N, Sonis ST, Bowen JM et al (2013) Emerging evidence on the pathobiology of mucositis. Support Care Cancer Off J Multinatl Assoc Support Care Cancer 21:3233–3241
4.
Tabbara IA, Zimmerman K, Morgan C, Nahleh Z (2002) Allogeneic hematopoietic stem cell transplantation: complications and results. Arch Intern Med 162:1558–1566CrossRefPubMed
5.
Ringden O, Labopin M, Ehninger G et al (2009) Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol 27:4570–4577CrossRef
6.
Ringden O, Le Blanc K (2005) Allogeneic hematopoietic stem cell transplantation: state of the art and new perspectives. APMIS Acta Pathol Microbiol Immunol Scand 113:813–830CrossRef
7.
Legert KG, Remberger M, Ringden O, Heimdahl A, Dahllof G (2014) Reduced intensity conditioning and oral care measures prevent oral mucositis and reduces days of hospitalization in allogeneic stem cell transplantation recipients. Support Care Cancer Off J Multinatl Assoc Support Care Cancer 22:2133–2140
8.
Ringden O, Erkers T, Aschan J et al (2013) A prospective randomized toxicity study to compare reduced-intensity and myeloablative conditioning in patients with myeloid leukaemia undergoing allogeneic haematopoietic stem cell transplantation. J Intern Med 274:153–162CrossRefPubMed
9.
10.
Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM (2008) Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol 62:33–41CrossRefPubMed
11.
Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM (2008) Serum levels of NFkappaB and pro-inflammatory cytokines following administration of mucotoxic drugs. Cancer Biol Ther 7:1139–1145CrossRefPubMed
12.
Holler E, Kolb HJ, Moller A et al (1990) Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 75:1011–1016PubMed
13.
von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R (1995) Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 181:1519–1526CrossRef
14.
von Freeden-Jeffry U, Solvason N, Howard M, Murray R (1997) The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7:147–154CrossRef
15.
16.
Silva A, Laranjeira AB, Martins LR et al (2011) IL-7 contributes to the progression of human T-cell acute lymphoblastic leukemias. Cancer Res 71:4780–4789CrossRefPubMed
17.
Teles R, Sakellari D, Teles F et al (2010) Relationships among gingival crevicular fluid biomarkers, clinical parameters of periodontal disease, and the subgingival microbiota. J Periodontol 81:89–98CrossRefPubMedCentralPubMed
18.
Garlet GP (2010) Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res 89:1349–1363CrossRefPubMed
19.
Ozkavaf A, Aras H, Huri CB et al (2000) Relationship between the quantity of gingival crevicular fluid and clinical periodontal status. J Oral Sci 42:231–238CrossRefPubMed
20.
Khaw A, Logan R, Keefe D, Bartold M (2014) Radiation-induced oral mucositis and periodontitis—proposal for an inter-relationship. Oral Dis 20:e7–e18CrossRefPubMed
21.
Svahn BM, Remberger M, Myrback KE et al (2002) Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood 100:4317–4324CrossRefPubMed
22.
Slavin S, Nagler A, Naparstek E et al (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91:756–763PubMed
23.
Ringden O, Ruutu T, Remberger M et al (1994) A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood 83:2723–2730PubMed
24.
Lundgren G, Wilczek H, Lonnqvist B, Lindholm A, Wahren B, Ringden O (1985) Acyclovir prophylaxis in bone marrow transplant recipients. Scand J Infect Dis Suppl 47:137–144PubMed
25.
Kallestal C, Matsson L (1989) Criteria for assessment of interproximal bone loss on bite-wing radiographs in adolescents. J Clin Periodontol 16:300–304CrossRefPubMed
26.
Organization WH (1979) WHO handbook for reporting results for cancer treatment. vol 48:1
27.
Sonis ST, Peterson DE, McGuire DB, Williams DA (2001) Prevention of mucositis in cancer patients. J Natl Cancer Inst Monogr 1–2
28.
Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST, Keefe DM (2009) Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemother Pharmacol 63:239–251CrossRefPubMed
29.
Sonis ST (2002) The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med Off Publ Am Assoc Oral Biologists 13:380–389CrossRef
30.
Sonis ST (2009) Mucositis: the impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol 45:1015–1020CrossRefPubMed
31.
32.
Tsilingaridis G, Yucel-Lindberg T, Modeer T (2012) T-helper-related cytokines in gingival crevicular fluid from adolescents with Down syndrome. Clin Oral Investig 16:267–273CrossRefPubMed
33.
Sparrelid E, Hagglund H, Remberger M et al (1998) Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection. Bone Marrow Transplant 22:795–800CrossRefPubMed
34.
Meirovitz A, Kuten M, Billan S et al (2010) Cytokines levels, severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer—a prospective pilot study. Radiat Oncol 5:16CrossRefPubMedCentralPubMed
35.
Chung B, Min D, Joo LW et al (2011) Combined effects of interleukin-7 and stem cell factor administration on lymphopoiesis after murine bone marrow transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 17:48–60CrossRef
36.
Schauer MC, Holzmann B, Peiper M, Friess H, Knoefel WT, Theisen J (2010) Interleukin-10 and −12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma. J Thorac Oncol 5:1849–1854CrossRefPubMed
37.
Remberger M, Ringden O, Markling L (1995) TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant 15:99–104PubMed
38.
Lamster IB, Ahlo JK (2007) Analysis of gingival crevicular fluid as applied to the diagnosis of oral and systemic diseases. Ann N Y Acad Sci 1098:216–229CrossRefPubMed
39.
Orlicek SL, Branum KC, English BK, McCordic R, Shenep JL, Patrick CC (1997) Viridans streptococcal isolates from patients with septic shock induce tumor necrosis factor-alpha production by murine macrophages. J Lab Clin Med 130:515–519CrossRefPubMed
40.
Ferra C, de Sanjose S, Gallardo D et al (1998) IL-6 and IL-8 levels in plasma during hematopoietic progenitor transplantation. Haematologica 83:1082–1087PubMed
41.
Mosmann TR, Kobie JJ, Lee FE, Quataert SA (2009) T helper cytokine patterns: defined subsets, random expression, and external modulation. Immunol Res 45:173–184CrossRefPubMed
42.
Uitto VJ (2003) Gingival crevice fluid—an introduction. Periodontology 2000(31):9–11CrossRef
Metadata
Title
The relationship between oral mucositis and levels of pro-inflammatory cytokines in serum and in gingival crevicular fluid in allogeneic stem cell recipients
Authors
Karin Garming Legert
Georgios Tsilingaridis
Mats Remberger
Olle Ringdèn
Anders Heimdahl
Tülay Yucel-Lindberg
Göran Dahllöf
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 6/2015
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-014-2538-z

Other articles of this Issue 6/2015

Supportive Care in Cancer 6/2015 Go to the issue

Original Article

Adverse breast cancer treatment effects: the economic case for making rehabilitative programs standard of care

Original Article

Caregiving among American Indians and Alaska Natives with cancer

Original Article

Hyponatremia as an independent prognostic factor in patients with terminal cancer

Original Article

The role of volunteers at an outpatient cancer center: how do volunteers enhance the patient experience?

Original Article

Tolerability of denosumab in metastatic solid tumor patients with renal insufficiency

Original Article

Outcome of chemotherapy extravasation in a large patient series using a standardised management protocol
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits