Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis.
The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.
Department of Immuno-Rheumatology, Hôpital Gui de Chauliac, Montpellier, France.
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D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D016207:Cytokines / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D015213:Neuroimmunomodulation / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology; D009490:Neurosecretory Systems / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011388:Prolactin / Q000502:physiology
D016207:Cytokines; D012739:Gonadal Steroid Hormones; D009479:Neuropeptides; D011388:Prolactin