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Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Clinical data and blood samples were collected from adults in Mozambique with <jats:italic>P. falciparum<\/jats:italic> infection, with (n\u2009=\u200970) and without (n\u2009=\u200961) HIV co-infection, from HIV-infected patients with similar symptoms without malaria (n\u2009=\u200958) and from healthy controls (n\u2009=\u200952). In vitro studies were performed in endothelial cells using hemozoin crystals.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>(i) IL-18 and IL-18bp were markedly up-regulated during falciparum malaria with particular high levels in malaria patients co-infected with HIV and severe malaria disease. (ii) In the malaria group as a whole, both IL-18 and IL-18bp were positively correlated with disease severity, parasitemia, and endothelial cell activation as assessed by vWF in plasma. (iii) Whereas there was no change in IL-18 levels in malaria patients co-infected with HIV during follow-up, the patients with malaria only had slightly increased IL-18 levels. Further, the IL-18pb levels declined and thereby contributed to an increase in IL-18\/IL-18bp ratio in all subgroups of malaria patients. (iv) IL-27, previously shown to be up-regulated in this malaria cohort, markedly induced a release of IL-18bp from endothelial cells in vitro, and notably, this presumably anti-inflammatory effect was counteracted by hemozoin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that the IL-18 system could be an important mediator in the immune pathogenesis during falciparum malaria, potentially also representing a target for therapy<jats:bold><jats:italic>.<\/jats:italic><\/jats:bold><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-021-06751-y","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T22:14:05Z","timestamp":1634595245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria"],"prefix":"10.1186","volume":"21","author":[{"given":"Kari","family":"Otterdal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aase","family":"Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika E.","family":"Michelsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Yndestad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Gregersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bente","family":"Halvorsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thor","family":"Ueland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Langeland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e5l","family":"Aukrust","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"issue":"5","key":"6751_CR1","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1093\/cid\/ciy934","volume":"69","author":"C Dobano","year":"2019","unstructured":"Dobano C, Nhabomba AJ, Manaca MN, Berthoud T, Aguilar R, Quinto L, et al. 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A signed consent or fingerprint was obtained from each patient or next of kin and from the healthy controls. Management of the patients was carried out according to the local standard of care by the hospital's doctors and staff.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1073"}}