title: Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model.
abstract: Inflammation is considered the underlying cause of numerous disorders, and the practice of taking antiinflammatories as diet supplements has become increasingly prevalent. This study addresses the bioavailablity of a well-established dietary antiinflammatory, curcumin, and examines its effect on adaptive immunity. Visceral leishmaniasis is a major parasitic disease which protection relies on cell-mediated immunity and production of nitric oxide. We found that long-term, low-dose, oral consumption of curcumin activates peroxisome proliferator-activated receptor-gamma, deactivates type 1 response, inhibits inducible nitric oxide synthase, and interferes with adaptive immunity to exacerbate the pathogenesis of Leishmania donovani infection in vivo. These in vivo effects can be correlated to activities on infected residential macrophages in vitro. Therefore, when reactive radicals generated from inflammation play the dominant role in elimination of pathogens, excessive use of the antioxidative supplements may compromise microbial defense. Nonetheless, it should be noted with equal importance that our finding, conversely, also strengthens the prospect that curcumin may alleviate type 1 response disorders.
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Nagasuresh
authors.initials: N
authors.lastname: Adapala
authors.forename: Marion M
authors.initials: MM
authors.lastname: Chan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000819:agonists; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047495:PPAR gamma; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin
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