Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?

OBJECTIVE

Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1beta, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements.

METHODS

We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA.

RESULTS

Untreated patients had high serum levels of IL-1beta and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1beta levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r = -0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores).

CONCLUSIONS

Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1beta and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.