Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration,
osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded
glycosphingolipids. To investigate the possible role of
cytokines in the systemic and local manifestations of established
Gaucher's disease,
interleukin-1 beta (IL-1 beta),
interleukin-6 (IL-6), tumour
necrosis factor-alpha (
TNF alpha) and
interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1
Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of
IL-6 and
IL-10 were significantly elevated in sera from patients with
Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of
TNF alpha or
IL-1 beta were identified.
IL-6 has been implicated in the development of localized
osteolysis in
multiple myeloma and in the development of
post-menopausal osteoporosis. High concentrations of
IL-6 in the serum of patients with
Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since
IL-6 and
IL-10 are important regulators of lymphocyte growth and differentiation, and
IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum
immunoglobulins, enhanced release of these
cytokines from pathological macrophages provides a pathological link between
Gaucher's disease and associated lympho-proliferative disorders.