Change of peripheral levels of pituitary hormones and cytokines after injection of interferon (IFN)-beta in patients with chronic hepatitis C.

Interferons (IFNs) are now in use worldwide for the treatment of chronic viral hepatitis. Unfortunately, various side effects of IFNs have been reported. Because cytokines, which include IFNs, can affect endocrine function, endocrinological abnormalities are sometimes observed in patients treated with IFNs. We examined the effects of IFN-beta on peripheral levels of pituitary and adrenal hormones and cytokines. Six million international units of IFN-beta dissolved in glucose solution was injected for 30 min. As a control study, glucose solution without IFN-beta was injected. Pituitary hormones (ACTH, GH, TSH, prolactin (PRL), LH, FSH, and arginine-vasopressin (AVP)), cortisol, and cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF), and interleukin-1 receptor antagonist (IL-1ra) were measured before and after IFN-beta injection. The study was carried out on 14 patients with chronic hepatitis type C who were under treatment with IFN-beta. All studies were performed when the patients were afebrile. None of the patients had any endocrine or autoimmune diseases. Plasma ACTH levels increased significantly at 60-120 min after IFN-beta injection compared with the levels before IFN-beta injection and in the control study using glucose injection. Plasma cortisol levels increased after IFN-beta injection, in parallel with plasma ACTH elevation. Serum GH levels increased significantly at 120 min after IFN-beta injection. All the increased hormones including ACTH, cortisol, and GH, were decreased at the end of the study-180 min after IFN-beta injection. Serum levels of TSH, PRL, LH, FSH, and AVP were not changed significantly by IFN-beta injection. Plasma IL-1 and TNF levels did not change after IFN-beta injection, while IL-6 and IL-1ra were elevated significantly. The increases in IL-6 and IL-1ra were gradual, reaching their peak levels at 180 min after IFN-beta injection. However there were no correlations between the hormones measured in this study and the levels of IL-6 or IL-1ra. It would seem that IFN-beta has direct or indirect stimulatory effects for ACTH and GH without mediation of the cytokines. These in vivo results are important for investigating the relationship between endocrine and cytokine systems in humans.