Acute interferon beta-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 (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.
Goebel
M U
MU
Department of Medical Psychology, Medical Faculty, University of Essen, Hufelandstr 55, 45122, Essen, Germany. marion.goebel@uni-essen.de
Baase
J
J
Pithan
V
V
Exton
M
M
Saller
B
B
Schedlowski
M
M
Limmroth
V
V
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D005434:Flow Cytometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D010919:Placebos; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D015850:Interleukin-6; D010919:Placebos; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000068576:Interferon beta-1b; D016899:Interferon-beta; D006854:Hydrocortisone