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Disorders in the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis have been reported in human and experimental visceral leishmaniasis,\u00a0but not yet in canine leishmaniasis. Cortisol is a steroid hormone that regulates several processes, including immune responses. This study investigated HPA axis disorders in dogs with visceral leishmaniasis and their link to clinical and immunological parameters. ELISA quantified serum levels of cortisol and adrenocorticotrophic hormone (ACTH) in 12 healthy dogs and 13 dogs with leishmaniasis. The expression of the enzymes inducible nitric oxide synthase (iNOS) and arginase\u20101 and programmed cell death protein\u20101 (PD\u20101) were evaluated by flow cytometry in peripheral blood mononuclear cells (PBMC). Additionally, serum levels of the cytokines interleukin (IL)\u20101\u03b2, IL\u20106, IL\u201010, IL\u201012, interferon\u2010gamma (IFN\u2010\u03b3), tumour necrosis factor\u2010alpha (TNF\u2010\u03b1), and transforming growth factor\u2010beta (TGF\u2010\u03b2) were quantified by capture Enzyme\u2010Linked Immunosorbent Assay (ELISA). Parasite load was quantified in peripheral blood and conjunctival swabs by real\u2010time polymerase chain reaction (qPCR). All parameters evaluated were correlated with serum cortisol. We observed an increase in cortisol, while ACTH levels were reduced in dogs with leishmaniasis. The expression of iNOS, arginase\u20101 and PD\u20101 was higher in the PBMC of dogs with leishmaniasis. Serum levels of the cytokines IL\u201010, IL\u20106, IL\u201012, and IFN\u2010\u03b3 were increased in dogs with leishmaniasis. Cortisol showed a negative correlation with PD\u20101 and IL\u201012. Our findings suggest that infection natural with\n                    <jats:italic>L. infantum<\/jats:italic>\n                    in dogs may induce dysregulation of the HPA axis, leading to elevated serum cortisol levels and modulation of the immune response, as it is associated with immunological markers involved in disease pathogenesis. These results contribute to a better understanding of the pathogenic mechanisms of the disease.\n                  <\/jats:p>","DOI":"10.1111\/pim.70062","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:53:57Z","timestamp":1770026037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cortisol Regulates PD\u20101 and IL\u201012 in Canine Leishmaniasis"],"prefix":"10.1111","volume":"48","author":[{"given":"Lucas Takeshi Siqueira","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Surgery and Animal Reproduction S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele Mitsue","family":"Umino","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Surgery and Animal Reproduction S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba 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