Increased in vitro bone resorption by monocytes in the hyper-immunoglobulin E syndrome.
Children with the hyper-immunoglobulinemia E syndrome are prone to bone fractures. We determined bone density in six patients with hyper-IgE syndrome using photon absorptiometry. All six patients had significantly reduced bone density compared with age- and sex-matched controls. The capacity of peripheral blood monocytes to degrade 45Ca-labeled bone in vitro was studied. The mean percent 45Ca release in four hyper-IgE patients (40.8 +/- 8.6) was significantly higher (p less than 0.01) than in ten age-matched healthy control subjects (7.1 +/- 2.6), seven age-matched patients with recurrent infections (7.9 +/- 1.6), or nine patients with severe atopic dermatitis and elevated serum IgE levels (5.8 +/- 1.3). Monocytes from four of four patients studied spontaneously released abnormally high levels of prostaglandin E2. Bone degradation by these monocytes was significantly reduced in the presence of 10(-6) M indomethacin in vitro. Administration of aspirin in vivo to two hyper-IgE patients reduced boned degradation by their monocytes to normal levels. These results suggest that monocytes from patients with hyper-IgE syndrome are activated to resorb bone via products of the prostaglandin synthase (cyclooxygenase) pathway. The activation of cells in the monocyte/macrophage family to resorb bone may contribute to the osteopenia observed in hyper-IgE syndrome.
Leung
D Y
DY
Division of Allergy, Children's Hospital, Boston, MA 02115.
Key
L
L
Steinberg
J J
JJ
Young
M C
MC
Von Deck
M
M
Wilkinson
R
R
Geha
R S
RS
D001241:Aspirin / Q000627:therapeutic use; D001862:Bone Resorption / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015232:Dinoprostone; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D006942:Hypergammaglobulinemia / Q000150:complications / Q000503:physiopathology*; D007073:Immunoglobulin E; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000502:physiology*; D010024:Osteoporosis / Q000150:complications* / Q000188:drug therapy; D011458:Prostaglandins E / Q000378:metabolism
D011458:Prostaglandins E; D007073:Immunoglobulin E; D015232:Dinoprostone; D001241:Aspirin; D006909:Hydroxyproline; D007213:Indomethacin