Interleukin 1β mediated calciotropic activity in serum of children with juvenile rheumatoid arthritis

Objective. To detect the presence and source of calciotropic activity in the serum of children with juvenile rheumatoid arthritis (JRA). Methods. Metabolic evaluation of an adolescent with polyarticular JRA and hypercalcemia/hypercalciuria included testing with a bone disc bioassay. The bioassay detects calciotropic activity (increased bone resorption or reduced bone formation) in serum. Interleukin 1 receptor antagonist (IL-1RA) was added to patient sera to test the role of IL-1β. The results in this index case prompted additional study in 9 children with JRA. Correlation of calciotropic activity with disease activity score, erythrocyte sedimentation rate (ESR), and urinary calcium excretion was by Spearman rank correlation. Results. Calciotropic activity was found in 2 consecutive samples from the index patient. This activity was eliminated by addition of IL-1RA (p < 0.001 compared to serum alone). Testing of the other 9 children showed calciotropic activity at least once in 7/9 and 10/15 samples studied. Addition of IL-1RA completely (6/8) or partially (2/8) neutralized calciotropic activity (p < 0.001 compared to serum alone) in the specimens available for testing. Calciotropic activity did not significantly correlate with disease activity score, ESR, or urine calcium. Conclusion. Our data indicate the presence of IL-1β mediated calciotropic activity in the sera of children with JRA, and suggest a role for IL-1β in JRA associated osteopenia.