Interleukin (IL)-4 and IL-13 inhibit the differentiation of murine osteoblastic MC3T3-E1 cells

Interleukin-4 (IL-4) inhibits the spontaneous and stimulated bone resorptio n resulting from the inhibition of osteoclast formation, as well as osteocl astic activity. Since IL-13 shares some biological properties with IL-4, it was recently reported that IL-13 inhibits bone resorption. The present stu dy was designed to determine the effects of murine IL-4 (IL-4) and murine I L-13 (IL-13) on the murine osteoblastic cell line MC3T3-E1. IL-4 and IL-13 stimulated H-3-thymidine incorporation in the MC3T3-E1 cells and its prolif eration in dose dependent manners. A spontaneous increase in alkaline phosp hatase (ALP) activity in the cells after plating was inhibited by IL-4 or I L-13, and both cytokines blunted an increase in ALP activity by human parat hyroid hormone (PTH) (1-34). PTH-stimulated cyclic AMP (cAMP) production wa s inhibited by pretreatment with IL-4 and IL-13 for 48 hr in dose dependent manners. Pretreatment with IL-4 and IL-13 for 48 hr caused a decrease in P TH-induced cAMP production at any stimulatory concentration. However, the e ffective dose (ED50) was unchanged by the pretreatment with these cytokines . Pretreatment with IL-4 and IL-13 did not modulate cAMP generation by fors kolin. In contrast, cAMP generation by PGE(2) is greater in the cells treat ed with the cytokines compared to those without the cytokines. These result s indicate that IL-4 and IL-13 act on MC3T3-E1 cells in the same manner, st imulating cell proliferation, but inhibiting cell differentiation. The inhi bition of osteoblast differentiation by IL-4 and IL-13 may be associated wi th a decrease in PTH actions on osteoblasts.