Thyroid dysfunction and abnormalities in
corticosteroid regulation were observed after clinical use of
cytokines (
IL2, IFN alpha), molecules with immunostimulating properties.
Interleukin 2 administration induces
hypothyroidism often associated with
anti-thyroglobulin and anti-thyroid microsomal antibody. All these features recall Hashimoto's
thyroiditis. Frequency of thyroid dysfunction during
immunotherapy varies according to authors between 20 and 40 percent of all patients treated. A correlation between thyroid dysfunction and response to
IL2 therapy was reported.
Hypothyroidism and
hyperthyroidism with development of anti-
TSH receptor antibody are observed after IFN alpha administration. An auto-immune aetiology of these thyroid side effects was suggested because fine needle aspirates of the thyroid of these patients, when available, revealed a mixed cellular infiltrate with lymphocytes and histiocytes and immunocytochemical staining showed strong
HLA-DR expression of all thyrocytes. Involvement of lymphokine activated killer (LAK) or direct effect of
cytokines on thyroid are also possible. After
intravenous injection of
IL2, a marked increase in
ACTH levels occurred, peaking at 4 hour with a comparable peak in
cortisol level at 5 hour. Expression of IL2-Receptor in pituitary cells suggests a direct action of
IL2 on anterior pituitary. Nevertheless, indirect action of
IL2 via induction of other
cytokines or possible secretion of
ACTH by activated lymphocytes, cannot be ruled out.
Testosterone serum levels decreased significantly after
IL2 or IFN alpha administration. It is noteworthy that these endocrine effects induced by
cytokines may modulate the clinical efficacy of these substances underlying the bi-directional communication between the immune and endocrine system.