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Multiple diagnoses are used for inflammatory conditions of the lactating breast, such as engorgement, blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, mastitis and white spots, which lack agreed or evidence-based aetiology, definitions and treatment. This is the first in a series of three articles which review the research literature concerning benign lactation\u2013related breast inflammation. This article investigates aetiological models. A complex systems perspective is applied to analyse heterogeneous and interdisciplinary evidence elucidating the functional anatomy and physiology of the lactating breast; the mammary immune system, including the human milk microbiome and cellular composition; the effects of mechanical forces during lactation; and the interactions between these. This analysis gives rise to a mechanobiological model of breast inflammation, in which very high intra-alveolar and intra-ductal pressures are hypothesized to strain or rupture the tight junctions between lactocytes and ductal epithelial cells, triggering inflammatory cascades and capillary dilation. Resultant elevation of stromal tension exerts pressure on lactiferous ducts, worsening intraluminal backpressure. Rising leucocyte and epithelial cell counts in the milk and alterations in the milk microbiome are signs that the mammary immune system is recruiting mechanisms to downregulate inflammatory feedback loops. From a complex systems perspective, the key mechanism for the prevention or treatment of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents a critical mass of mechanical strain and rupture of the tight junctions between lactocytes and ductal epithelial cells.<\/jats:p>","DOI":"10.1177\/17455065221075907","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T01:35:00Z","timestamp":1644802500000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Re-thinking benign inflammation of the lactating breast: A mechanobiological model"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-9816","authenticated-orcid":false,"given":"Pamela","family":"Douglas","sequence":"first","affiliation":[{"name":"School of Nursing and Midwifery, Griffith University, Brisbane, QLD, Australia"},{"name":"General Practice Clinical Unit, The University of Queensland, Brisbane, QLD, Australia"},{"name":"Possums & Co., Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,2,13]]},"reference":[{"key":"bibr1-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-1295"},{"key":"bibr2-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1315i"},{"key":"bibr3-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1089\/bfm.2021.29181.ams"},{"key":"bibr4-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1177\/0890334420907898"},{"key":"bibr5-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1177\/17455065211031480"},{"key":"bibr6-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32585-5"},{"key":"bibr7-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32573-9"},{"key":"bibr8-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.6016"},{"key":"bibr9-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.8254"},{"key":"bibr10-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1111\/risa.13204"},{"key":"bibr11-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1016\/j.midw.2017.12.007"},{"key":"bibr12-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.12153"},{"key":"bibr13-17455065221075907","first-page":"88","volume":"2018","author":"Kapoor V","journal-title":"MJA"},{"key":"bibr14-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1177\/0194599820925415"},{"key":"bibr15-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.0153"},{"key":"bibr16-17455065221075907","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.5710"},{"key":"bibr17-17455065221075907","doi-asserted-by":"crossref","unstructured":"Malchodi L, Wagner K, Susi A, et al. 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