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Avascular necrosis of the femoral head (ANFH) is commonly observed in patients treated withexcessive glucocorticoid (GC). Single administration of lipopolysaccharide (LPS) has shown toinduce immune stimulatory factors. However, the effect of repeated administration of LPS onGC-induced ANFH has not been studied. Thus, the purpose of this study was (i) to examinethe cytokine profile induced by repeated LPS administrations and (ii) to test the effect ofrepeated LPS treatments on GC-induced ANFH. A mouse necrosis model of ANFH wasdesigned by chronic GC administration with co-treatment of LPS. Mice body weights in theLPS/prednisolone (PDN) co-treated group were lower than that of the untreated controlgroup, but spleen weights were greater than the control group. The levels of IL-6, TNFα, andIL-33 in the liver and spleen of the LPS/PDN group were lower than the untreated controlgroup, whereas TNFα level in the femoral head of the LPS/PDN group increased. Collectively, the effect of repeated LPS on the pathogenesis of GC-induced ANFH wasassociated with the TNFα level in the femoral head, but the pathogenesis did not correspondto cytokine levels in immune tissues.

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