RESUMEN
A male infant with malignant osteopetrosis was treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Therapy with 1 alpha-hydroxyvitamin D3 increased the serum calcium level despite the markedly elevated serum level of 1 alpha, 25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression.
Asunto(s)
Hidroxicolecalciferoles/uso terapéutico , Interferón gamma/uso terapéutico , Osteopetrosis/terapia , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Humanos , Hidroxicolecalciferoles/farmacología , Lactante , Interferón gamma/farmacología , Masculino , Osteopetrosis/diagnóstico , Osteopetrosis/metabolismo , Proteínas RecombinantesRESUMEN
Macrophages and osteoclasts derive from related cell lines. In osteopetrotic mutants the function of osteoclasts is greatly reduced compared to that in normal animals or children and macrophage function is variably affected depending upon the mutation. To further explore macrophage function in osteopetrosis we examined the regulation of cyclic AMP production in macrophages from mutants and normal littermates of the osteopetrotic stock incisors-absent (ia) in the rat. Surface stimulation by latex particles of elicited peritoneal macrophages from normal or osteopetrotic (ia) mutant rats caused an identical increase in the accumulation of cyclic AMP. This effect was inhibited in normal animals by coincubation of macrophages with calcitonin (CT) but this inhibition was either absent or less marked in macrophages from mutant littermates. In contrast to human monocytes preincubation of rat macrophages with pertussis toxin did not relieve this inhibition. This implies that rat peritoneal macrophages respond to CT by a different mechanism. These results demonstrate altered macrophage function in osteopetrotic animals and may be functionally related to the reduced CT binding previously described in ia osteoclasts. Furthermore, the coexistence of reduced function of macrophages and osteoclasts in the ia mutation suggests that macrophages and osteoclasts share a common progenitor.