Acute and chronic neuroendocrine effects of interferon‐β 1a in multiple sclerosis

Bergh, Florian Then; Kümpfel, Tania; Yassouridis, Alexander; Lechner, Christian; Holsboer, Florian; Trenkwalder, Claudia

doi:10.1111/j.1365-2265.2006.02725.x

Cited by 16 publications

(11 citation statements)

References 41 publications

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“…Also, HPA axis function seems to adapt to continuous INF-β administration in a way that cortisol levels normalize over the course of prolonged treatment (e.g. three months, one year) [19] [27]. In our study, treated RRMS patients and treatment naïve RRMS patients did not significantly differ in AUC awakening which further supports the hypothesis that circadian HPA axis changes cannot be exclusively explained by treatment effects.…”

Section: Discussionsupporting

confidence: 83%

“…Acute administration of Interferon-β (INF- β) has shown to cause significant changes in cortisol release within MS patients [19] and HC subjects [27]. It is therefore possible that HPA axis abnormalities seen in MS could be explained by treatment effects.…”

Section: Discussionmentioning

confidence: 99%

“…Relapsing-remitting (RRMS) as well as secondary-progressive (SPMS) MS patients were studied in order to identify a possible link between circadian cortisol release patterns and disease course as well as disease duration. Finally, we expected diurnal cortisol patterns to be associated with treatment [19], disease progression [15], affective symptoms [16], [17] and perceived stressful experience [6].…”

Section: Introductionmentioning

confidence: 99%

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Cortisol Awakening Response Is Linked to Disease Course and Progression in Multiple Sclerosis

et al. 2013

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ObjectivesDysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation which is associated with a series of methodological caveats. Knowledge of circadian cortisol patterns and cortisol awakening response (CAR) is still limited.MethodsA total of 77 MS patients (55 relapsing-remitting MS (RRMS)/22 secondary-progressive MS (SPMS)) as well as 34 healthy control (HC) subjects were enrolled. Diurnal cortisol release was assessed by repeated salivary cortisol sampling. Neurological disability was rated by the Kurtzke’s Expanded Disability Status Scale (EDSS). Depressive symptoms and perceived stress were assessed by self-report measures.ResultsRRMS but not SPMS patients differed in circadian cortisol release from HC subjects. Differences in cortisol release were restricted to CAR. Treated and treatment naïve RRMS patients did not differ in CAR. In a RRMS follow-up cohort (nine months follow-up), RRMS patients with EDSS progression (≥0.5) expressed a significantly greater CAR compared to HC subjects. RRMS patients with a stable EDSS did not differ from HC subjects. Neither depressive symptoms nor perceived stress ratings were associated with CAR in RRMS patients. In a step-wise regression analysis, EDSS at baseline and CAR were predictive of EDSS at follow-up (R2 = 67%) for RRMS patients.ConclusionsCircadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cortisol Awakening Response Is Linked to Disease Course and Progression in Multiple Sclerosis

et al. 2013

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“…Some evidence suggests that prolonged treatment with IFNβ may affect HPA axis activity in MS,38 39 and interferon α administration has been associated with a flattening of cortisol profiles in other patient groups 40. Thus we more closely examined the role of DMTs on HPA axis activity in our sample.…”

Section: Resultsmentioning

confidence: 99%

Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression

Gold

Krüger

Ziegler

et al. 2011

Journal of Neurology, Neurosurgery & Psychiatry

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Objective: Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, we examined the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity for depression and fatigue in patients with relapsing-remitting MS (RRMS).Methods: HPA axis function and frequency of stimulated cytokine (IFNγ and TNFα) producing T cells was measured cross-sectionally in 44 female patients with RRMS. All subjects completed a neurological exam, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and self-report questionnaires. Results: Ten patients met diagnostic criteria for MDD. MS patients with comorbid MDDshowed normal morning but elevated evening salivary cortisol levels resulting in a flattened slope. While higher frequency of cytokine producing CD8+ T cells was also seen in MS patients with MDD, these markers were more closely associated with fatigue than depression. Conclusions:This study supports a role of HPA axis hyperactivity for major depression in MS. In addition, inflammatory and neuroendocrine factors may differentially mediate fatigue and depressive symptoms.

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“…In addition to the modulating effects on the immunesystem Interferon-β (IFN-β) may also have acute effects on the pituitary gland with increased secretion of adrenocorticotrophin (ACTH), prolactin and growth hormone (GH) [1,2]. Moreover a recent investigation reported a modest increase in serum levels of insulin-like growth factor I (IGF-I) in IFN-β-treated patients with multiple sclerosis (MS) suggesting a persistent effect of IFN-β on the GH-IGF-I axis [3].…”

Section: Introductionmentioning

confidence: 99%

Interferon-β treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

Andreassen¹,

Frystyk²,

Miller³

et al. 2010

Scandinavian Journal of Clinical and Laboratory Investigation

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We describe a 34-year-old female treated with IFN-β for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT). There were no clinical features of acromegaly. A 5-day profile showed higher GH levels on the 3 days following IFN-β injections. Total and bioactive IGF-I were also elevated but did not fluctuate. Four weeks off IFN-β normalized suppression of GH during OGTT but did not reduce serum IGF-I or bioactive IGF-I. In conclusion, IFN-β treatment mimicked acromegaly biochemically. The changes were partially reversible.

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Acute and chronic neuroendocrine effects of interferon‐β 1a in multiple sclerosis

Abstract: Marked neuroendocrine effects occur in response to IFN-beta in multiple sclerosis. Upon prolonged treatment, these effects partially adapt, and HPA axis hyperactivity is reduced. Prospective studies to determine the relation to individual treatment response can be based on these findings.

Cited by 16 publications

References 41 publications

Cortisol Awakening Response Is Linked to Disease Course and Progression in Multiple Sclerosis

Cortisol Awakening Response Is Linked to Disease Course and Progression in Multiple Sclerosis

Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression

Interferon-β treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

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