This Is MS Multiple Sclerosis Knowledge & Support Community

Psychoneuroendocrinology. 2002 Nov;27( 8 ):881-92. Related Articles, Links

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

Goebel MU, Baase J, Pithan V, Exton M, Saller B, Schedlowski M, Limmroth V.

Department of Medical Psychology, Medical Faculty, University of Essen, Hufelandstr 55, 45122, Essen, Germany. marion.goebel@uni-essen.de

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.

PMID: 12383450 [PubMed - indexed for MEDLINE]

OddDuck wrote:Is this why for the most part, the interferons are NOT prescribed for progressive MS?

Immunol Lett. 2001 Jan 15;75(3):191-7.
Interferon-beta1a administration results in a transient increase of serum amyloid A protein and C-reactive protein: comparison with other markers of inflammation.

Boylan MT, Crockard AD, Duddy ME, Armstrong MA, McMillan SA, Hawkins SA.

Department of Microbiology and Immunobiology, The Queen's University of Belfast, Microbiology Building, Royal Group of Hospitals Trust, Grosvenor Road, BT12 6BA, Belfast, Northern Ireland, UK. m.boylan@qub.ac.uk

Putative markers of inflammation such as serum beta2-microglobulin and neopterin have been shown to be transiently upregulated following interferon-beta (IFN-beta) administration to multiple sclerosis (MS) patients. However, to date the role of the important inflammatory mediators serum amyloid A protein (SAA) and C-reactive protein (CRP) have not been described. Here we show that SAA but not CRP is elevated in relapsing-remitting MS patients compared to normal healthy individuals, and furthermore that both are transiently upregulated following intramuscular injection with IFN-beta1a (Avonex). This pattern of expression was found to parallel that of beta2-microglobulin and neopterin following injection and was mirrored by a selective activation of peripheral monocytes with respect to upregulation of receptors known to be involved in the inflammatory response (HLA-DR, CD16 and CD86). Injection of saline solution intramuscularly to six healthy control individuals did not produce a similar upregulation of any of the inflammatory markers investigated. Following IFN-beta1a injection, all inflammatory responses were attenuated at week 12 of therapy in comparison to those following the initial injection in a group of follow-up patients. In addition, IFN-beta1a injected on a weekly basis did not produce a sustained modulation of any of the markers investigated in patients treated for 32 weeks.

....IL6, like IL1 , stimulates the synthesis of ACTH (Corticotropin ) in the pituitary. Glucocorticoids synthesized in response to ACTH inhibit the production of IL6, IL1 and TNF in vivo, thus establishing a sort of negative feedback loop between the immune system and neuroendocrine functions. In astrocytes IL6 induces the synthesis of NGF.

IL6 is a B-cell differentiation factor in vivo and in vitro (see also: BCDF ) and an activation factor for T-cells (see also: Cell activation ). In the presence of IL2 IL6 induces the differentiation of mature and immature T-cells into cytotoxic T-cells. IL6 also induces the proliferation of thymocytes and probably plays a role in the development of thymic T-cells.
….

Intracerebral overexpression of IL6 in Transgenic mice has been shown to be associated with neurological syndromes the severity of which correlate with the levels of IL6 expression. These mice are characterized by runting, tremor, neurodegeneration, astrocytosis, angiogenesis , and induction of acute-phase proteins production, suggesting a direct pathogenic role of IL6 in inflammatory, infectious, and neurodegenerative CNS diseases (see also: Inflammation ).

Brett et al have used a transgenic mouse model to express IL6 in brain astrocytes. They demonstrate an extensive break down of the blood brain barrier. Depending upon expression levels and age the animals show a leptomeningeal inflammatory infiltrate, vacuolated astrocytic foot processes and endothelial abnormalities, parenchymal inflammation , gliosis, spongiform change, axonal degeneration and macrophage accumulation.