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Interleukin‐4 inhibits spontaneous and parathyroid hormone‐related protein‐stimulated osteoclast formation in mice
Author(s) -
Nakano Yoichiro,
Watanabe Kenichi,
Morimoto Isao,
Okada Yosuke,
Ura Kazumi,
Sato Kanji,
Kasono Keizo,
Nakamura Toshitaka,
Eto Sumiya
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650091005
Subject(s) - osteoclast , endocrinology , medicine , parathyroid hormone related protein , bone resorption , chemistry , in vivo , parathyroid hormone , calcium , ratón , resorption , receptor , biology , microbiology and biotechnology
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‐1α, 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 μg/day. When infused with 0.6 nmol/day of PTHrP(1‐34) in ICR mice, rmIL‐4 at a dose of 1 or 5 μg/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.