Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include ␣-melanocyte-stimulating hormone (␣-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of ␣-MSH (1-13), ␣-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor ␣ (TNF-␣), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon ␥ (IFN-␥). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS ؉ IFN-␥, microglia increased release of ␣-MSH. Production of TNF-␣, IL-6, and NO was greater in activated microglia after immunoneutralization of endogenous ␣-MSH. The results suggest that ␣-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders. J. Leukoc. Biol. 63: 740-745; 1998.

No abstract

Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan ® , correlates with chronic vascular complications in a cohort of T2DM. Methods:We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan ® and extensive evaluation of macrovascular and microvascular diabetic complications.Results: Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication, 19% a macrovascular complication (prior myocardial infarction and/or ischaemic stroke) and 33% a microvascular one (26% chronic kidney disease [CKD]; 16% retinopathy; 6% neuropathy). In all, 171 (72%) patients had CAP ≥ 248dB/m (ie hepatic steatosis), whereas 83 (21%) patients had LSM ≥ 7.0/6.2 kPa (M/XL probes) (significant liver fibrosis). CAP was not associated with any macro/microvascular complications, whereas LSM ≥ 7.0/6.2 kPa was independently associated with prior cardiovascular disease (adjusted OR 3.3, 95%CI 1.2-8.8; P = .02) and presence of microvascular complications (adjusted OR 4.2, 95%CI 1.5-11.4; P = .005), mainly CKD (adjusted OR 3.6, 95%CI 1.3-10.1; P = .01) and retinopathy (adjusted OR 3.7, CI 95% 1.2-11.9; P = .02). Neither diabetes duration nor haemoglobin A1c differed according to CAP or LSM values.Conclusion: Significant fibrosis, detected by FibroScan ® , is independently associated with increased prevalence of macrovascular and microvascular complications, thus opening a new scenario in the use of this tool for a comprehensive evaluation of hepatic and vascular complications in patients with T2DM.