Increased serum levels of osteoclast activating cytokines as a possible reason for osteoporosis in patients with common variable immunodeficiency (CVID)

Increased serum levels of interleukin-6 (IL-6) have repeatedly been reported in patients suffering form CVID, and have been blamed to contribute to the osteoporotic process observed in these patients. In fact, IL-6 is considered to be a major factor in osteoporosis in post-menopausal women and other conditions accompanied with loss of sex hormones. Recent investigations identified other cytokines using the gp130 signal transducer molecule, namely oncostatin M, leukemia inhibitory factor, ciliary neurotrophic factor, and most prominently interleukin-ll (IL-11) as major osteoclast-activating factors. Here we show that the extremly elevated levels of IL-6 reported in earlier works may be caused in part by IL-11. Also, we report dramatically increased levels of IL-11 bioactivity and protein content in the sera of patients with CVID. We consider this to be additional proof that cytokines acting through gp 130 play an essential role in osteoporosis in these patients and to warrant an investigation of other gp 130-activating cytokines in CVID.