Effects of interleukin-2 on bone resorption and natural immunity in osteopetrotic (ia) rats

Cells of the immune system and the cytokines they produce have been shown to function in the regulation of bone turnover. Incisors absent (ia) osteopetrotic rats demonstrate defects in natural immunity and bone resorption, even though they have excess numbers of both natural killer (NK) cells and osteoclasts. In an attempt to correct these defects, mutant (ia) and normal rats were infused with 3 x 10(4)U recombinant interleukin-2 (rIL-2)/day for 14 days using osmotic minipumps. The effects of IL-2 on natural immune function and bone resorption were evaluated after the infusion period. The percentage of NK cells in the spleen after treatment was quantitated by phenotypic analysis using monoclonal antibodies and flow cytometry. The elevated levels of NK cells normally seen in ia mutants were reduced to normal in the IL-2-infused rats. NK cell activity was evaluated by the 51Cr release assay and found to be enhanced to normal killing levels in the IL-2-treated mutants. The defects in NK function are corrected by IL-2 therapy. Likewise, the bone resorption defect appears to be corrected by the IL-2 infusions. The bone marrow cavity size was significantly increased in the IL-2-treated mutants compared with control mutants. Additionally, the percentage of osteoclasts exhibiting normal morphology was significantly increased in the IL-2-treated mutants. The bone density of the caudal vertebrae, evaluated by gray-scale analysis of x-rays, was found to be reduced in the IL-2-treated mutants. Interleukin-2 corrects both the bone resorption and natural immune defects in the ia mutation.