Iloprost modulates the immune response in systemic sclerosis.

BACKGROUND: Iloprost has been suggested to possess anti-inflammatory and immunomodulating actions and it is widely use as a vasodilatator in systemic sclerosis (SSc). In this study we evaluate the effect of iloprost on immune response in SSc patients. To this extend we enrolled 15 women affected by SSc and infused iloprost for 5 days. The effect of iloprost on T cells and monocytes was measured by flow cytometry, Real time PCR and measuring cytokines production in vivo and in vitro by ELISA. RESULTS: Our results demonstrate that Iloprost reduces T cell and TNF alpha production both in vivo and in vitro. It reduces T regulatory cells number, but increases their activity after immune stimulation. It increases serum IL-2 and this increase persists 28 days after the last infusion, also RANKL was increased both in vivo and in vitro. We observed no effect on IFN gamma production. CONCLUSIONS: These results suggest that iloprost has anti-inflammatory and immunomodulating effects, reducing TNF alpha production by T cells and the number of T regulatory cells and increasing IL-2 and RANKL.

Role of iron metabolism and oxidative damage in postmenopausal bone loss.

It has been suggested that iron-deficient rats have lower bone mass than iron-replete animals, but a clear association between bone and iron repletion has not been demonstrated in humans. A growing body of evidences also suggests a relation between lipid oxidation and bone metabolism and between iron metabolism and LDL oxidation. Iron availability to cells also depends on haptoglobin (Hp) phenotypes. Hp has also important antioxidant properties according to its phenotype, hence we evaluate whether Hp phenotype could influence bone density, iron metabolism and lipid oxidation. This cross-sectional study enrolled 455 postmenopausal women affected by osteoporosis (260) or not (195). Bone mineral density, markers of bone and iron metabolism, levels of oxidized LDL (oxLDL) and Hp phenotype were measured in all the subjects. Hp 1.1 and 2.2 frequency was higher and Hp 2.1 was lower in the patients with fragility fractures (80) compared with the controls. We therefore evaluate different Hp phenotypes as risk or protective factors against fragility fracture: Hp 2.1 is a protective factor against fracture while 1.1 is an important and 2.2 a moderate risk factor for fragility fractures. Lower serum iron was associated with elevated transferrin in patients with Hp 1.1; moreover patients had relative iron deficiency compared with the controls and fractured patients had higher level of oxLDL. We found that both iron metabolism and oxLDL varies according to Hp phenotypes and are predictive of bone density. Our data indicate that Hp 2.1 is a protective factor for fragility fractures, depending on its role on iron metabolism and its antioxidant properties.