Cytokines in Gaucher disease: Role in the pathogenesis of bone and pulmonary disease

Gaucher disease (GD) is the most frequently encountered lysosomal storage disease caused by inborn defects of the membrane-bound lysosomal enzyme, acid β-glucosidase or glucocerebrosidase. This defective activity causes an accumulation of glucocerebroside (glucosylceramide) in the lysosomes of cells derived from the monocyte/macrophage lineage. Glucocerebroside-engorged cells, termed Gaucher cells, infiltrate various organs, leading to multisystemic abnormalities. The mechanisms by which systemic and organ-specific involvement is propagated or initiated remain unclear. Studies are increasingly recognizing the role of immune dysregulation and inflammation in the pathogenesis of Gaucher disease. Many cytokines have been reported as mediators of tissue damage in Gaucher disease. Bone and lung disease are serious causes of morbidity in non neuronopathic Gaucher disease. The progress in the understanding of the pathogenesis or relevant mechanism(s) of Gaucher disease is providing insights into additional therapeutic targets, enabling the potential for optimized patient outcomes with the use of adjunctive or supplemental agents.