biostudies-literatureAlves THHS | NIH | National Institute of Dental and Craniofacial Research (NIDR)NIDCR NIH HHSNCATS NIH HHSNIAID NIH HHSNHLBI NIH HHSHHS | NIH | National Center for Advancing Translational Sciences (NCATS)HHS | NIH | National Institute of Allergy and Infectious DiseasesHHS | NIH | NCI | Division of Cancer Prevention, National Cancer Institute (DCP, NCI)HHS | NIH | National Center for Advancing Translational SciencesHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)HHS | NIH | NCI | Division of Cancer Prevention, National Cancer InstituteHHS | NIH | National Heart, Lung, and Blood InstituteNCI NIH HHSHHS | NIH | National Institute of Dental and Craniofacial Researche2507092122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12595481biostudies-literatureUnknown122(44)Inflammasome initiates inflammation via the maturation of interleukin-1 beta (IL-1β). Periodontitis is a prevalent, male-biased disease characterized by inflammation-driven bone loss, yet the mechanism(s) of this sex bias is unknown. This study explored whether enhanced inflammasome represents a causal mechanism for this bias. Analyses of three separate human studies (>6,200 samples) show that males have significantly higher IL-1β in the gingival crevicular fluid than females during health and periodontitis. This pattern is experimentally reproduced with different versions of the ligature-induced periodontitis mouse model where males show greater IL-1β secretion than females. The inflammasome drives bone resorption in males but not females as revealed by analyses of inflammasome gene-deletProceedings of the National Academy of Sciences of the United States of AmericaInflammasome targeting for periodontitis prevention is sex dependent.PMC12595481DE029625R21 DE029625K01 DE027087R01 DE032830R35 CA232109U19 AI067798HHSN268201700004IUL1TR002489-03S2DE032830R37 AI029564R01 AI029564R01 AI158314R01 DE029200HHSN268201700002IR01 AI153265AI029564P30 CA016086R00 DE023584HHSN268201700002CHHSN268201700004CAI153265DE0234804AI158314AI067798UL1 TR002489UL1TR002489HHSN268201700003IHHSN268201700005IHHSN268201700001IHHSN268201700005CR56 AI029564HHSN268201700001CHHSN268201700003CR56 AI158314DE027087CA232109DE029200Swanson KVTing JPYPreisser JSAlves TGill HSPreisser HLietzan ADZhang SDivaris KBrickey WJSantos PCPWrobel JAWebster-Cyriaque JChang JSeaman WTFreire MPirih FQMin HYBeck JSyed MSusin CVias NPHu DMorelli TMarchesan JTMoss KGirnary MSStyner MMakhanova NfalseInflammasome targeting for periodontitis prevention is sex dependent.Inflammasome initiates inflammation via the maturation of interleukin-1 beta (IL-1β). Periodontitis is a prevalent, male-biased disease characterized by inflammation-driven bone loss, yet the mechanism(s) of this sex bias is unknown. This study explored whether enhanced inflammasome represents a causal mechanism for this bias. Analyses of three separate human studies (>6,200 samples) show that males have significantly higher IL-1β in the gingival crevicular fluid than females during health and periodontitis. This pattern is experimentally reproduced with different versions of the ligature-induced periodontitis mouse model where males show greater IL-1β secretion than females. The inflammasome drives bone resorption in males but not females as revealed by analyses of inflammasome gene-delet2025-01-01T00:00:00Z2025 Nov2026-06-06T01:28:42.71Z2026-05-24T03:11:37.054ZS-EPMC125954814114467210.1073/pnas.2507092122