Interleukin-33 serum levels in postmenopausal women with osteoporosis.

There are many cytokines involved in the pathogenesis of osteoporosis. So far IL-33 involvement in osteoporotic patients has not yet been studied. IL-33 is a pro-inflammatory cytokine which mediates several immune functions; its involvement in a wide range of diseases, such as atopic dermatitis, asthma, and rheumatoid arthritis, is now emerging. In view of the crucial role of this cytokine in inflammation and bone remodeling, we measured IL-33 levels in the serum of postmenopausal women with osteoporosis. In 50 postmenopausal osteoporotic patients and 28 healthy postmenopausal control women, serum IL-33 levels were measured by enzyme linked immunosorbent assay. In both patients and controls the bone mineral density (BMD) was measured by double-energy X-ray absorptiometry (DXA). Vitamin D, calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH) serum levels, as well as bone turnover markers, such as C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type 1 procollagen (P1NP) were also evaluated. In postmenopausal osteoporotic women IL-33 levels were significantly lower compared to healthy controls (3.53 ± 2.45 vs. 13.72 ± 5.39 pg/ml; P = 0.009) and positively correlated respectively with serum PTH (rho = 0.314; P = 0.026) and P1NP (rho = 0.373; P = 0.011) levels, while a statistically significant inverse correlation was observed between serum IL-33 and CTX levels (rho = -0.455; P = 0.002). Our results thus suggest that IL-33 represents an important bone-protecting cytokine which may be of therapeutic benefit in treating bone resorption.

Psoriasis Induced by Anti-Tumor Necrosis Factor Alpha Agents: A Comprehensive Review of the Literature.

Tumor necrosis factor alpha (TNF-α) inhibitors revolutionized the management of patients affected by autoimmune diseases such as inflammatory bowel diseases, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. The biologic agents targeted to block TNF-α such as infliximab, adalimumab, certulizumab pegol, etanercept, and golimumab, have a good safety profile; however, with increasing, broader, and prolonged use, patients could be exposed to an increased risk of adverse reactions including a wide spectrum of dermatological conditions of different etiology and morphology. Among these, of particular interest is the development of skin immune-mediated diseases that seem to be the consequence of the paradoxical inflammation induced by anti-TNF-α therapy. The majority of these lesions are identified as psoriasiform with three main morphologies and different frequency: pustular psoriasis, signs of psoriasis, and guttate; although erythrodermic or inverted psoriasis, among others, may be observed with less frequency. The increased incidence of these dermatological immune-mediated lesions highlight the importance of the skin as a main target of the side effect of anti-TNF-α agents, while the immunopathogenetic hypothesis of these paradoxical effects are quite intriguing. The aim of this review is to collect and to analyze existing knowledge to better understand the pathogenetic mechanism of these complications and suggest new fields of investigation, improve therapeutic strategies of autoimmune diseases, and prevent and/or better address such complications.

An overview of environmental risk factors in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease with a complex and multifactorial pathogenesis, characterized by excessive collagen deposition and vasculopathy, leading to skin fibrosis and involvement of internal organs. Regarding the aetiology of SSc, our current knowledge is still limited; however, as for other autoimmune syndromes, the disease is probably caused by both endogenous and exogenous factors. Among the exogenous factors, in the past decades, several environmental exposures, including occupational exposure to pollutants, chemicals and hand-arm vibrations as well as infections, silicone and use of drugs, have been suggested to play a role in the development of SSc. The following review analyzes the most recent literature to examine the relationship between environmental exposures and SSc.

Increased levels of interleukin 31 (IL-31) in osteoporosis.

BACKGROUND: Several inflammatory cytokines play a key part in the induction of osteoporosis. Until now, involvement of the Th2 cytokine interleukin-31 (IL-31) in osteoporosis hadn't yet been studied. IL-31 is a proinflammatory cytokine mediating multiple immune functions, whose involvement in a wide range of diseases, such as atopic dermatitis, inflammatory bowel diseases and cutaneous lymphomas, is now emerging. Given the important role of IL-31 in inflammation, we measured its serum levels in postmenopausal osteoporotic patients. METHODS AND RESULTS: In fifty-six postmenopausal females with osteoporosis and 26 healthy controls, bone mineral density (BMD) measurements were performed by using calcaneal quantitative ultrasound (QUS) technique, confirmed at the lumbar spine and hip by dual energy X-ray absorptiometry (DXA). Both patients and controls were divided according to age (less or more than 65 years) and disease severity (T-score levels and presence of fractures). Serum IL-31 levels were measured by ELISA technique. Osteoporotic patients exhibited elevated levels of serum IL-31 compared with healthy controls (43.12 ± 6.97 vs 29.58 ± 6.09 pg/ml; p < 0.049). IL-31 expression was higher in over 65 years old patients compared to age-matched controls (45 ± 11.05 vs. 17.92 ± 5.92; p < 0.01), whereas in younger subjects no statistically significant differences were detected between patients and controls (37.91 ± 6.9 vs 32.08 ± 8.2). No statistically significant differences were found between IL-31 levels in patients affected by mild (T-score > -3) compared to severe (T-score < -3) osteoporosis (59.17 ± 9.22 vs 37.91 ± 10.52), neither between fractured and unfractured osteoporotic women (33.75 ± 9.16 vs 51.25 ± 8.9). CONCLUSIONS: We showed for the first time an increase of IL-31 serum levels in postmenopausal women with decreased BMD. Although they did not reflect the severity of osteoporosis and/or the presence of fractures, they clearly correlated with age, as reflected by the higher levels of this cytokine in aged patients.

Glucocorticoids in patients with rheumatic diseases: friends or enemies of bone?

Increased bone resorption and enhanced risk of osteoporotic fractures are often reported in patients with diseases having immune system involvement, mainly inflammatory rheumatic diseases, for which glucocorticoids are more often prescribed because of their powerful antinflammatory effects. Among secondary osteoporosis, glucocorticoid-induced osteoporosis is the most common and severe form, and up to now prolonged glucocorticoid therapy has been considered the most important osteoporotic risk factor in rheumatic patients. However, it is now clear that the pathogenesis of osteoporosis in inflammatory rheumatic diseases is mediated by several factors. In particular, new discoveries within osteoimmunology concerning the complex relationship between bone and immunity, suggest that inflammation itself, through proinflammatory and osteoclastogenic cytokine overexpression, promotes bone resorption leading to increased skeletal fragility. Therefore, by controlling systemic inflammation, it is also possible to reduce the loss of bone mass which accompanies rheumatic diseases. From this point of view, we critically revisit the effects of glucocorticoids on bone in rheumatic diseases, in which they should be seen not just as an enemy of the bone health but eventually as a potential therapeutic tool capable of reducing the risk of osteoporosis by controlling disease activity and inflammation.