Abstract
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.
Highlights
Lnterleukin-33 (IL-33), a 30-kDa protein, is a cytokine expressed by mainly stromal cells and upregulated following pro-inflammatory stimulation
IL-1 itself is a stimulator of osteoclast activity and prompts osteoblast production of cytokine receptor activator of NF-kB ligand (RANKL), the main positive controller of osteoclastogenesis
There was a significant positive correlation in all patients with osteoporosis between serum levels of IL-33 and parathyroid hormone (PTH)(Fig. 2), as well as between serum levels of IL-33 and P1NP (Fig. 3), whereas a significant negative correlation was observed between serum levels of IL-33 and CTX (Fig. 4)
Summary
Lnterleukin-33 (IL-33), a 30-kDa protein, is a cytokine expressed by mainly stromal cells and upregulated following pro-inflammatory stimulation. Described as an inducer of Th2 cytokine production[1], IL-33 can function as a traditional cytokine, as an alarmin and as a nuclear factor controlling gene transcription. It exerts its biological effects by interacting with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP); both these receptors are largely expressed, especially by innate immune and T helper 2 (Th2) cells. Osteoporosis occurs when the balance between bone resorption, carried out by osteoclasts, and bone formation, mediated by osteoblasts, is www.nature.com/scientificreports/. IL-1 itself is a stimulator of osteoclast activity and prompts osteoblast production of cytokine receptor activator of NF-kB ligand (RANKL), the main positive controller of osteoclastogenesis. IL-18, produced by osteoblasts and macrophages, inhibits osteoclast formation while has a mitogenic effect on osteoblasts[13]
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