Immunocytochemical Localisation of Interleukin-1α and Interleukin-6 in Thyroid Tissues from Patients with Neoplastic or Autoimmune Thyroid Disorders

Abstract

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.

A Role for IL-15 in Driving the Onset of Spontaneous Autoimmune Thyroiditis?

“…Not surprisingly, considering the implication of T cell-mediated cytotoxic processes in the pathogenesis of Hashimoto's thyroiditis after the lymphoid infiltration of the thyroid, the proinflammatory cytokines IL-1␤, IL-6, and IL-8 have all been shown to be expressed in the thyroids of patients suffering from the disease (26,(33)(34)(35)(36). This report shows that these cytokines are expressed in the thyroids of OS chickens before the onset of the lymphoid infiltration.…”

Interleukin 24 is induced by the RET/PTC3 oncoprotein and is an autocrine growth factor for epithelial cells

“…Some of these, such as IL1, IL6, IL8 and TNFa can be induced even from normal thyroid cells, indicating that cytokines may not only contribute to various thyroid cancers but may also serve to support the homeostatic control of cell survival at precancerous stages (Rasmussen, 2000). Tumor tissue or tumorderived cell lines from differentiated carcinomas release GCSF, GMCSF, IL1a, IL4, IL6, IL8, IL10, MCP1 and/ or TNFa (Tohyama et al, 1992;Kayser et al, 1995;Nakada et al, 1996;Basolo et al, 1998;Kurebayashi et al, 2000;Scarpino et al, 2000) and undifferentiated thyroid carcinomas produce GROa, GCSF, GMCSF, and IL1a, IL4, IL6, IL8, IL10, and/or TNFa (Enomoto et al, 1990;Yoshida et al, 1992;Aust and Scherbaum, 1996;Basolo et al, 1998;Stassi et al, 2003), although, in either case, very little is known about when in tumor development these factors are made or what their purpose may be. Whereas no single biochemical pathway has been identified that explains factor production by thyroid cells, we previously demonstrated that an alternative form of activated RET kinase (RP3) can induce secretion of large amounts of Mcp1 and Gmcsf, a property dependent on the function of the tyrosine kinase domain (Russell et al, 2003).…”

Plasma Selectin Levels in Patients with Graves'Disease.

“…The reason why plasma sP-Selectin levels increased in patients with untreated Graves' disease was not so clear. We thought that thyroid hormones as well as some cytokines such as interleukin-1 alpha, which was demonstrated in thyroid follicular epithelial cells [11], affected the expression, secretion and degradation of P-Selectin, which was similar to polymorphonuclear elastase [12], and that thyroid hormones might cause the secretion of a soluble form of P-Selectin as a result of alternative splicing [13]. Although sE-and sL-Selectin levels, not sP-Selectin, were noticeably increased in patients with Graves' disease before treatment with methimazole [14], there were some differences in the duration of follow up of the patients and of the quantity of methimazole administered, and their antibody by Bender MedSystems used for ELISA may be different from ours by Takara Co.…”