Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein-stimulated osteoclast formation in mice.
We examined the in vivo effects of recombinant murine IL-4 (rmIL-4) on spontaneous and stimulated mouse osteoclast formation. EC-GI cells, which produce PThrP and IL-1 alpha, were explanted in nude mice. These EC-GI cell-bearing nude mice developed hypercalcemia (4.90 +/- 0.68 mM), and the calcium levels were decreased to near normal (3.48 +/- 0.73 mM, p < 0.05) at day 3 by continuous infusion of rmIL-4 at a dose of 7 micrograms/day. When infused with 0.6 nmol/day of PTHrP(1-34) in ICR mice, rmIL-4 at a dose of 1 or 5 micrograms/day for 3 days caused a marked inhibitory effect on hypercalcemia induced by PTHrP(1-34) (3.73 +/- 0.56-2.54 +/- 0.14 mM, p < 0.01). However, rmIL-4 alone did not change the serum calcium in mice. Histomorphometric analysis revealed that rmIL-4 inhibits both spontaneous and PTHrP(1-34)-stimulated osteoclast formation in mice, with a decrease in osteoclastic surface and in the number of osteoclasts per mm bone surface, respectively. We conclude that IL-4 inhibits spontaneous and stimulated bone resorption resulting from inhibition of osteoclast formation and modulates the development of humoral hypercalcemia of malignancy.
Nakano
Y
Y
First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.
Watanabe
K
K
Morimoto
I
I
Okada
Y
Y
Ura
K
K
Sato
K
K
Kasono
K
K
Nakamura
T
T
Eto
S
S
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D002118:Calcium / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000473:pathology; D005260:Female; D005269:Femur / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015918:Infusion Pumps, Implantable; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000633:toxicity*; D011506:Proteins / Q000633:toxicity*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C079957:parathyroid hormone-related peptide (1-36); D015847:Interleukin-4; D002118:Calcium