{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:41Z","timestamp":1760146241928,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research (NIHR) Official Development Assistance (ODA)","award":["GHR 16\/136\/29"],"award-info":[{"award-number":["GHR 16\/136\/29"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Epidemiological, histological, and immunogenetic studies suggest that podoconiosis (a non-infectious tropical lymphoedema affecting approximately 4 million people globally) is an HLA class II-associated inflammatory condition that develops in response to an unknown trigger found in volcanic red clay soils. Silicate particles of the kaolinite and aluminum types have been identified in femoral lymph node biopsy samples from endemic area residents, suggesting a possible role in the pathogenesis of podoconiosis. We measured in vitro peripheral blood mononuclear cell cytokine responses (TNF-\u03b1, IL-1\u03b2, and IFN-\u03b3) to stimulation with the minerals kaolinite, chlorite, and beryllium sulfate (all at 100 \u00b5M) using ELISA. Real time PCR was used to measure gene expression of signature cytokines in fresh whole blood, comparing podoconiosis patients and endemic healthy controls. Our results showed that the levels of TNF-\u03b1 and IL-1\u03b2 from in vitro cell cultures were significantly higher in unstimulated samples from patients compared to controls (p = 0.04 and p = 0.005, respectively). The minerals kaolinite and chlorite induced two and three-fold higher levels of IL-1\u03b2 following 24 h of stimulation in healthy controls compared to patients, respectively. We did not find significant differences in mRNA expression of the cytokine genes assayed, though a slight fold increment in IL-1\u03b2 and TGF-\u03b2 was observed. In conclusion, our data suggest that the immune system is in a state of persistent activation in vivo in podoconiosis patients, and additional studies of immune regulation and exhaustion are needed to further characterize immune dysfunction in the pathogenesis of the disease. A better understanding of the underlying processes could lead to the development of a \u2018biosignature\u2019 detectable in the early reversible stages that could ultimately contribute to the elimination of this preventable, disabling, neglected tropical disease.<\/jats:p>","DOI":"10.3390\/tropicalmed9110252","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T11:31:57Z","timestamp":1729596717000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in Cytokine Expression at Baseline and in Response to Mineral Stimulation by Peripheral Blood Mononuclear Cells from Podoconiosis Cases and Healthy Control Individuals"],"prefix":"10.3390","volume":"9","author":[{"given":"Mikias","family":"Negash","sequence":"first","affiliation":[{"name":"Brighton and Sussex Centre for Global Health Research, Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton BN1 9PX, UK"},{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"},{"name":"Department of Medical Laboratory Science, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tigist","family":"Girma","sequence":"additional","affiliation":[{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-2100","authenticated-orcid":false,"given":"Menberework","family":"Chanyalew","sequence":"additional","affiliation":[{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawit H.","family":"Alemayehu","sequence":"additional","affiliation":[{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Alcantara","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Centre for Global Health Research, Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton BN1 9PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2796-7468","authenticated-orcid":false,"given":"Gail","family":"Davey","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Centre for Global Health Research, Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton BN1 9PX, UK"},{"name":"School of Public Health, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary J.","family":"Boyton","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London, London W2 1PG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-6192","authenticated-orcid":false,"given":"Daniel M.","family":"Altmann","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation, Imperial College London, London W12 0NN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-7525","authenticated-orcid":false,"given":"Melanie J.","family":"Newport","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Centre for Global Health Research, Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton BN1 9PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawleigh","family":"Howe","sequence":"additional","affiliation":[{"name":"Armauer Hansen Research Institute, Addis Ababa P.O. Box 1005, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/0035-9203(76)90078-X","article-title":"The association of endemic elephantiasis of the lower legs in East Africa with soil derived from volcanic rocks","volume":"70","author":"Price","year":"1976","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_2","first-page":"151","article-title":"Non-filarial elephantiasis--confirmed as a geochemical disease, and renamed podoconiosis","volume":"26","author":"Price","year":"1988","journal-title":"Ethiop. Med. J."},{"key":"ref_3","first-page":"23","article-title":"Endemic elephantiasis of the lower legs in the United Cameroon Republic","volume":"33","author":"Price","year":"1981","journal-title":"Trop. Geogr. 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