Acute interferon beta-1b administration alters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects

• Published in: Psychoneuroendocrinology Vol. 27; no. 8; pp. 881 - 892
• Main Authors: Goebel, M U, Baase, J, Pithan, V, Exton, M, Saller, B, Schedlowski, M, Limmroth, V
• Format: Journal Article
• Language: English
• Published: England 01.11.2002
• Subjects: Adjuvants, Immunologic - pharmacology; Adrenal Glands - drug effects; Adrenal Glands - physiology; Adult; Blood Pressure - drug effects; Body Temperature - drug effects; Cross-Over Studies; Cytokines - blood; Flow Cytometry; Heart Rate - drug effects; Humans; Hydrocortisone - blood; Hypothalamus - drug effects; Hypothalamus - physiology; Interferon beta-1b; Interferon-beta - pharmacology; Interleukin-10 - blood; Interleukin-6 - blood; Kinetics; Leukocyte Count; Lymphocyte Subsets; Male; Pituitary Gland - drug effects; Pituitary Gland - physiology; Placebos; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - analysis
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/S0306-4530(01)00099-3

It has been suggested that the immune-endocrine communication plays an important role in development and progression of multiple sclerosis (MS). Interferon beta (IFN beta-1b) treatment is the therapy of choice in patients suffering from relapsing remitting or secondary chronic progressive multiple sclerosis. While typical adverse events of IFN beta-1b treatment such as flu-like symptoms or fatigue are well studied, little is known about the acute changes in the immune and neuroendocrine system. Therefore, we analyzed the short-term effects of IFN beta-1b on cortisol, epinephrine, norepinephrine, prolactin and growth hormone (GH) plasma levels before and 4, 8 and 24 h after IFN beta-1b administration in healthy subjects. Moreover, we determined heart rate, blood pressure, body temperature, leukocyte and lymphocyte subsets and plasma levels of interleukin (IL)-1 beta, IL-6, IL-10 and tumor necrosis factor (TNF)-alpha. IFN beta-1b led to an increase in body temperature and heart rate, and in parallel, elevated cortisol, prolactin and GH plasma levels at 4 and 8 h after IFN beta-1b injection. There were no significant alterations in blood pressure, norepinephrine or epinephrine plasma levels. Simultaneously, IFN beta-1b injection led to an immediate granulocytosis while concomitantly decreasing peripheral lymphocytes, especially natural killer (NK) cells. At the same time, IL-6, IL-10 and TNF-alpha plasma levels showed an overall increase. Overall, cytokine administration exerts strong stimulatory effects on the hypothalamic-pituitary-adrenal (HPA)-axis that may contribute to the side effects of IFN beta-1b therapy and affect the efficacy of IFN beta-1b treatment.