{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:27:31Z","timestamp":1765355251050},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T00:00:00Z","timestamp":1100649600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T00:00:00Z","timestamp":1100649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>The process of elimination of intracellular pathogens, such as <jats:italic>Leishmania<\/jats:italic>, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-<jats:italic>Leishmania<\/jats:italic> humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>A significant decrease in plasma Zn was observed in all three patient groups (p &lt; 0.01 for LCL and ML, p &lt; 0.001 for VL), as compared to controls, but only VL (7\/10) and ML (1\/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p &lt; 0.001) but not in ML, and was strongly correlated to anti-<jats:italic>Leishmania<\/jats:italic> IgG (Spearman r = 0.65, p = 0.0028). Cu\/Zn ratios were highest in patients with deficient cellular (VL&lt;&lt;LCL&lt;ML) and exacerbated humoral (VL&gt;LCL&gt;ML) immune response. <jats:italic>Ex vivo<\/jats:italic> production of parasite-induced IFN-\u03b3 was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). <jats:italic>In vitro<\/jats:italic>, increased Cu levels inhibited IFN-\u03b3 production.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-\u03b3 production.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2334-4-50","type":"journal-article","created":{"date-parts":[[2005,1,12]],"date-time":"2005-01-12T22:25:51Z","timestamp":1105568751000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Zinc\/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study"],"prefix":"10.1186","volume":"4","author":[{"given":"Johan","family":"Van Weyenbergh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gis\u00e9lia","family":"Santana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Argemiro","family":"D'Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Anibal F","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos H","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar M","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldina","family":"Barral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoel","family":"Barral-Netto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,11,17]]},"reference":[{"key":"135_CR1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0035-9203(01)90223-8","volume":"95","author":"P Desjeux","year":"2001","unstructured":"Desjeux P: The increase in risk factors for leishmaniasis worldwide. 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