Cytokines Explored in Saliva and Tears from Radiated Cancer Patients Correlate with Clinical Manifestations, Influencing Important Immunoregulatory Cellular Pathways
Lara A. Aqrawi,
Xiangjun Chen,
Håvard Hynne,
Cecilie Amdal,
Sjur Reppe,
Hans Christian D. Aass,
Morten Rykke,
Lene Hystad Hove,
Alix Young,
Bente Brokstad Herlofson,
Kristine Løken Westgaard,
Tor Paaske Utheim,
Hilde Kanli Galtung,
Janicke Liaaen Jensen
Affiliations
Lara A. Aqrawi
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Xiangjun Chen
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Håvard Hynne
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Cecilie Amdal
Section for Head and Neck Oncology, Oslo University Hospital, 0379 Oslo, Norway
Sjur Reppe
Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway
Hans Christian D. Aass
Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway
Morten Rykke
Department of Cariology and Gerodontology, Faculty of Dentistry, University of Oslo, 0455 Oslo, Norway
Lene Hystad Hove
Department of Cariology and Gerodontology, Faculty of Dentistry, University of Oslo, 0455 Oslo, Norway
Alix Young
Department of Cariology and Gerodontology, Faculty of Dentistry, University of Oslo, 0455 Oslo, Norway
Bente Brokstad Herlofson
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Kristine Løken Westgaard
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Tor Paaske Utheim
Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway
Hilde Kanli Galtung
Department of Oral Biology, Faculty of Dentistry, University of Oslo, 0316 Oslo, Norway
Janicke Liaaen Jensen
Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, 0317 Oslo, Norway
Although radiotherapy is a common form of treatment for head and neck cancer, it may lead to tissue damage in the salivary and lacrimal glands, possibly affecting cytokine expression in the gland fluid of treated individuals. Cytokine profiles in saliva and tear fluid of 29 radiated head and neck cancer patients and 20 controls were screened using a multiplex assay. Correlations between cytokine expression and clinical oral and ocular manifestations were examined, and cellular pathways influenced by these cytokines were assessed using the Functional Enrichment Analysis Tool. Significantly elevated cytokines identified in patient saliva were CCL21, IL-4, CX3CL1, CCL2, CXCL1 and CCL15. Many of these cytokines correlated positively with objective signs of oral dryness, and reduced saliva production in the patients. Although CCL21 and IL-4 levels were significantly lower in patient tear fluid, they correlated with subjective ocular symptoms. These increased salivary cytokines affected pro-inflammatory and apoptotic cellular pathways, including T cell signalling, several interleukin signalling pathways, TNF and TGF-β receptor signalling, and the apoptotic p53 pathway. In conclusion, the upregulated salivary cytokines identified suggest an interplay between innate and adaptive immunity, affecting immunoregulatory cellular pathways. Whether this is due to late effects of radiotherapy or tissue repair remains to be investigated.
