IL-14 and IL-16 are expressed in the thyroid of patients with either Graves' disease or Hashimoto's thyroiditis.
OBJECTIVE
Cytokines have an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The aim of the current study was to analyse the expression of interleukin (IL)-14 and IL-16 in the thyroid tissue of patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) or multinodular goitre (MNG) and in that of normal individuals, in patients' intrathyroidal CD4(+) and CD8(+) T cells, and in patient and normal cultured thyroid follicular cells.


METHODS
The expression of IL-14 and IL-16 mRNA and protein was investigated using reverse transcription-polymerase chain reaction (RT-PCR) amplification, and Western blotting and ELISAs, respectively.


RESULTS
IL-14 mRNA expression was detected in thyroid tissue from 8/9 GD, 3/4 HT and 3/13 MNG patients and 1/6 normal individuals, and IL-16 mRNA expression in thyroid tissue from 9/9 GD, 4/4 HT and 9/13 MNG patients and 4/6 normal individuals. IL-14 mRNA expression was detected in intrathyroidal CD4(+) and CD8(+) T cells from 2/2 GD and 2/2 HT patients, while IL-16 mRNA was detected in samples from 1/2 HT patients but not in those from either patient with GD. IL-14 and IL-16 mRNA expression was found in thyroid follicular cells derived from 2/2 patient with GD and 1/1 normal individual. IL-14 protein was detected in thyroid tissue from 6/6 GD, 1/1 HT and 0/6 MNG patients and 0/6 normal individuals, and IL-16 protein in thyroid tissue from 6/6 GD, 1/1 HT and 1/6 MNG patients and 0/6 normal individuals. Expression of IL-14 protein was stimulated in thyroid follicular cells derived from two patients with GD and one normal individual by peripheral blood mononuclear cell (PBMC)-conditioned medium. Treatment of thyrocytes from two patients with GD and one normal individual with PBMC-conditioned medium and tumour necrosis factor (TNF)-α stimulated IL-16 protein expression. In normal thyrocytes, IL-16 protein synthesis was induced also by IL-1β, IL-17A, IL-4 and transforming growth factor (TGF)-β.


CONCLUSIONS
The data provide evidence that the intrathyroidal production of IL-14 and IL-16 is associated with the pathogenesis of autoimmune thyroid disease. Thyroid follicular cells display the ability to express IL-14 and IL-16 mRNA and can be stimulated to express IL-16 protein, by a panel of cytokines, and IL-14 protein, by as yet unidentified factors.
Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK.
Elizabeth Helen
EH
Kemp
Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Ramzi A
RA
Ajjan
Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK.
Russell A
RA
Metcalfe
Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK.
Philip F
PF
Watson
Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK.
Anthony P
AP
Weetman
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D006111:Graves Disease / Q000276:immunology / Q000378:metabolism*; D050031:Hashimoto Disease / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019410:Interleukin-16 / Q000378:metabolism*; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism; D013972:Thyrotropin; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D019410:Interleukin-16; C488100:TXLNA protein, human; D033921:Vesicular Transport Proteins; D013972:Thyrotropin