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

It has been suggested that the immune-endocrine communication plays an important role in development and progression of multiple sclerosis (MS). Interferon beta (IFNbeta-1b) treatment is the therapy of choice in patients suffering from relapsing remitting or secondary chronic progressive multiple sclerosis. While typical adverse events of IFNbeta-1b treatment such as flulike 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 IFNbeta-1b on cortisol, epinephrine, norepinephrine, prolactin and growth hormone (GH) plasma levels before and 4, 8 and 24 It after IFNbeta-1b administration in healthy subjects. Moreover, we determined heart rate, blood pressure, body temperature, leukocyte and lymphocyte subsets and plasma levels of interleukin (IL)-1beta, IL-6, IL- 10 and tumor necrosis factor (TNF)-alpha. IFNbeta-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 It after IFNbeta-1b injection. There were no significant alterations in blood pressure, norepinephrine or epinephrine plasma levels. Simultaneously, IFNbeta-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 IFNbeta-1b therapy and affect the efficacy of IFNbeta-1b treatment. (C) 2002 Elsevier Science Ltd. All rights reserved.