Anemia of
inflammation (AI) is associated with inflammatory diseases, and
inflammation-induced
iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in
periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both
periodontitis patients and a mouse model of
ligature-induced experimental
periodontitis showed that
periodontitis was associated with lower levels of
hemoglobin and hematocrit with evidence of systemic
inflammation (increased white blood cell levels) and evidence of
iron restriction (low serum
iron along with a high serum
hepcidin and
ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal
therapy improved the
anemia status and
iron metabolism disorders. Furthermore, the increased level of
hepcidin and significant correlation between
hepcidin and key indicators of
iron metabolism emphasized the pivotal role of
hepcidin in the pathogenesis of
periodontitis-related AI. Administration of the
signal transducer and activator of transcription 3 (STAT3) inhibitors
Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that
periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of
periodontitis-related AI. Our study will provide new insights into the systemic effects of
periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.