Background and PurposeBone resorption induced by interleukin‐1β (IL‐1β) and tumour necrosis factor (TNF‐α) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation‐induced bone resorption can be impaired byIL‐4 andIL‐13. The aim was to investigate if expression ofB1andB2kinin receptors can be affected byIL‐4 andIL‐13.Experimental ApproachWe examined effects in a human osteoblastic cell line (MG‐63), primary human gingival fibroblasts and mouse bones byIL‐4 andIL‐13 onmRNAand protein expression of theB1andB2kinin receptors. We also examined the role ofSTAT6byRNAinterference and usingStat6‐/‐mice.Key ResultsIL‐4 andIL‐13 decreased themRNAexpression ofB1andB2kinin receptors induced by eitherIL‐1β orTNF‐α inMG‐63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2agonist) or des‐Arg10‐Lys‐bradykinin (B1agonist) in gingival fibroblasts pretreated withIL‐1β was impaired byIL‐4. Similarly, the increased binding ofB1andB2ligands induced byIL‐1β was decreased byIL‐4. In calvarial bones fromStat6‐deficient mice, and in fibroblasts in whichSTAT6was knocked down bysiRNA, the effect ofIL‐4 was decreased.Conclusions and ImplicationsThese data show, for the first time, thatIL‐4 andIL‐13 decrease kinin receptors in aSTAT6‐dependent mechanism, which can be one important mechanism by which these cytokines exert their anti‐inflammatory effects and impair bone resorption.