SP0111 How neuro endocrine immunology impact rheumatic diseases?

Abstract

The Neuro Endocrine Immune Network (NEI) is the most important communication- system in human body to mantain the health status. NEIRD evaluate the relationships between NEI and Rheumatic and Musculoskeletal Diseases (RMDs). The altered interaction between the nervous system, the immune/inflammatory cells and the endocrine system plays an important role in the pathophysiology of autoimmunity and chronic inflammation. The involvement of the adrenal steroid hormones in the immune response is fundamental and follow a circadian rhythm (circadian rhythm studies obtained the Nobel Prize for Medicine in 2017). As Matter of fact, the nocturnal ability of the NEI system to mount an efficient immune and inflammatory response, with related clinical consequences, is matter of important chronotherapeutical approaches with exogenous steroids, in particular with glucocorticoids (GCs) (their siscovery obtained the Nobel Prize in 1950 and still a pillar in the treatment of RMDs and not only). Other important steroid hormones involved in the NEI are the sex hormones (estrogens.E2 OH-metabolites are potent enhancers of cell proliferation) and the d-hormone (steroidal hormone structure of the final metabolite of Vitamin D). Clinical observations indicate a strong influence of the neuroendocrine system on immune function and vice versa in chronic inflammatory rheumatic diseases. The influence of hormones and neuronal pathways happens before and after the outbreak of the disease. Very recent data demonstrate the modulatory role of estrogens on epigenetic mechanisms (ie 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 oestrogen 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. We have started a large study on epigenetic and pregnancy on patients with RMDs such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). On the other hand, the disease process with an activated immune system influences several hormonal and neuronal pathways. In addition, the energy bottleneck leads to important disease sequelae such as sickness behaviour/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. New therapeutic strategies should respect these findings because rheumatic patients die earlier due to the mentioned disease sequelae. It is suggested that disease sequelae must be treated more consequently because they are inherent to chronic inflammatory systemic diseases (possible evolution for some of them in cancer). Therapeutic strategies in this field of NEIRD 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 utilisation of demonstrated concepts.