Raised serum levels of interleukin-8 and interleukin-18 in relation to bone metabolism in endogenous Cushing's syndrome

Objective: It is well known that patients with endogenous Cushing's syndrome (CS) have decreased bone mass and enhanced risk for osteoporotic fractures, secondary to decreased bone formation and increased bone resorption. Immunological mediators, such as cytokines, have recently been shown to influence bone metabolism, and in the present study we examined serum levels of several cytokines, with known or potential effects on bone homeostasis, in 33 consecutive recruited untreated CS patients and 33 age-, sex- and body mass index-matched healthy controls. Methods: Cytokine levels were measured by enzyme immunoassay and bone mass by dual-energy X-ray absorptiometry. Results: Our main findings were (i) interleukin (IL)-8 and IL-18 levels were significantly increased in CS patients compared with controls. (ii) Levels of both IL-8 and IL-18 were positively correlated to serum cortisol. (iii) For serum levels of the 'classical' resorptive cytokines, i.e. IL-6 and tumor necrosis factor alpha, no significant differences were found between CS patients and controls. (iv) Raised IL-18 levels were correlated with decreased osteocalcin levels in CS patients. Conclusions: Our results demonstrated that CS patients have markedly elevated levels of the proinflammatory cytokines IL-8 and IL-18 in spite of high levels of the immunosuppressive hormone cortisol. These cytokines may be involved in the pathogenesis of disturbed bone homeostasis in CS.