Neuroendocrine Immunology – Rheumatic Diseases
In 2001, Drs. Rainer Straub and Maurizio Cutolo, established experts in the field of neuroendocrine immunology of autoimmune and rheumatic diseases, published a large overview on the role of diverse neural and hormonal factors in rheumatoid arthritis.
In the last decade, Maurizio Cutolo, president of the European League against Rheumatism (EULAR) has also organized the first five international conferences on neuroendocrine immune basis of the rheumatic diseases.
In the May 2013 issue of Seminars in Arthritis and Rheumatism Drs. Straub and Cutolo, together with Drs. J. Bijlsma and A. Masi published a 10-year update on these issues.
Their focus was specifically on various aspects of the neuroendocrine-immune dysfunction in chronic musculoskeletal diseases. They review new fundamental and clinical data, accumulated over the last 10 years. Importantly, these experts summarize and group new evolving concepts in this field that may offer novel insights into the pathogenesis of rheumatic diseases.
According to the authors, these new concepts may provide the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets.
Source: Semin Arthritis Rheum, 2013 May 31. doi: 10.1016/j.semarthrit.2013.04.008. [Epub ahead of print]
Updates
In a 2018 EULAR Projects in investigative rheumatology M. Cutolo discussed ‘How neuro endocrine immunology impact rheumatic diseases?’ He outlined recent data demonstrating the modulatory role of estrogens on epigenetic mechanisms (i.e. DNA methylation and gene upregulation). For example, differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER have been shown, and provide new insights by which estrogen can modulate endothelial function. This point mighty be crucial in autoimmune diseases like systemic sclerosis (SSc) a disease prevalent in females and that start from damaged endothelium.
Importantly, he also discussed that an activated immune system influences several hormonal and neuronal pathways, and leads to important disease sequelae. This includes sickness behavior/fatigue/ depressive symptoms, sleep disturbances, anorexia and malnutrition, bone loss, muscle wasting and cachectic obesity, insulin resistance with hyperinsulinemia (insulin-like growth factor–1 resistance), dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, elevated sympathetic tone, hypertension and volume overload, decreased parasympathetic tone, inflammation–related anaemia, and finally circadian (circannual) rhythms of symptoms.
Moreover, therapeutic strategies are slowly developing. Low-dose glucocorticoid therapy as supplementation of the “small adrenal engine”, chronotherapy with glucocorticoids (night release) and vitamin D supplementation are the best examples of the successful
In a 2024 review article by Rainer H. Straub and Maurizio Cutolo provide a history of psycho-neuro-endocrine immune interactions in rheumatic diseases. Background: Neuroendocrine immunology describes the influence of neuronal pathways with neurotransmitters or endocrine glands with hormones on immune functions. Originally, this portrays the efferent influence of the brain on immune cells making use of connecting factors (neurotransmitters, especially steroid hormones).
Historically, neuronal pathways with the sensory nervous system and the autonomic nervous system (sympathetic; parasympathetic: n. vagus) were described before hormonal pathways came on stage, which led to the sequence of presentation in this article.The following areas and sections are included: (1) the sensory nervous system, (2) the sympathetic nervous system, (3) the vagus nerve, (4) steroid hormones (glucocorticoids, androgens, progesterone, estrogens, and the vitamin D hormone), (5) afferent pathways involved in fatigue, anxiety, insomnia, and depression (includes pathophysiology), and (6) evolutionary medicine and energy regulation – an umbrella theory.
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