Metals, autoimmunity, and neuroendocrinology: Is there a connection?

Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects

“…We could speculate that Ni exposure/allergy may lead to pituitary damage of an inflammatory nature. In fact, it is known that pituitary size reduction often represents the consequence of various types of hypophysitis [61] and that there is a strong association between SNAS and the increased systemic inflammation [37,39], also confirmed in our study population, where the presence of Ni allergy was positively correlated with several inflammatory markers. Of note, nonallergic subjects with radiological finding of ES were younger than the allergic counterpart (35.6 ± 17.9 years old compared to 52.8 ± 6.3 years old, respectively), suggesting that Ni exposure/allergy may lead to pituitary damage only in the long term.…”

“…First, Ni allergy is much more common in patients with obesity compared to the general population [35], and it is even more widespread among obese patients with worse metabolic profiles [36]; moreover, obese patients sensitized to Ni have a significantly lower baseline insulin-like growth factor 1 (IGF-1) level and a blunted growth hormone (GH) dynamic response compared to nonallergic ones [36]. The contribution of Ni allergy to fat mass excess could be immune-mediated, since both SNAS [37] and obesity [38] share an enhanced systemic inflammatory response as a fundamental pathogenetic mechanism; furthermore, it is known that exposure to different metals, such as Ni, can act as a trigger of autoimmune disorders, eventually leading to neurotoxicity [39]. Emerging evidence also indicates a direct role of Ni in altering specific metabolic pathways, and preclinical studies have recently shown that Ni may influence energy metabolism and glucose homeostasis [40][41][42][43][44][45].…”

Cadmium Body Burden and Inflammatory Arthritis: A Pilot Study in Patients from Lower Silesia, Poland

“…Namely, elevated exposure to metal compounds can modify cytokine production and alter the profile of pro- and anti-inflammatory factors. It may impair cell-mediated and/or humoral immunity and, consequently, lead to the manifestation and/or exacerbation of autoimmune disease symptoms [ 31 ]. There are reports indicating that cadmium exposure increases serum levels of pro-inflammatory cytokines [ 66 , 67 ].…”

“…Similar relationships have been observed by other authors [ 27 , 28 , 29 , 30 ]. There are indications that exposure to metals (including cadmium) may cause autoimmunity and epigenetic effects, thereby contributing to the incidence and prevalence of autoimmune diseases [ 31 , 32 ]. Some metal compounds modify cytokine production, leading to an imbalance between CD4 Th1 and Th2 cell activation and altering the pro- and anti-inflammatory cytokine profiles.…”

“…Some metal compounds modify cytokine production, leading to an imbalance between CD4 Th1 and Th2 cell activation and altering the pro- and anti-inflammatory cytokine profiles. This immune dysregulation can result in impaired cell-mediated immunity and/or aberrant humoral immunity, and, consequently, an autoimmune disease [ 31 ]. The influence of cadmium on the development of IA may, therefore, be related to the toxic effect on the immune system and its dysregulation.…”