TY - JOUR
T1 - Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model
AU - Adapala, Nagasuresh
AU - Chan, Marion M.
N1 - Funding Information:
This study was supported by NIH Grant R01 AI 45555, and fundings from American Institute for Cancer Research and CAFT of Rutgers University to Marion Chan. Experimental protocols used in this study were approved by the Temple University Institutional Animal Care and Use Committee (IACUC). We thank Dr Joe Shih, Division of Biometrics, The Cancer Institute of New Jersey, for performing statistic analyses, Dr Samuel Spadone, Dr Hyung Hee Kim, Ms Andrea Rossi, and Mr Rodger Brown for various assistance and Mr Gregory Harvey for editing the manuscript. Above all, the intellectual support from Dr Dunne Fong is greatly appreciated.
PY - 2008/12
Y1 - 2008/12
N2 - 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-γ, 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.
AB - 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-γ, 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.
KW - Antiinflammatories
KW - Curcumin
KW - Leishmania donovani
KW - Nitric oxide
KW - Peroxisome proliferator-activated receptor-γ
KW - T helper 1 immunity
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U2 - 10.1038/labinvest.2008.90
DO - 10.1038/labinvest.2008.90
M3 - Article
C2 - 18794851
AN - SCOPUS:56649094498
SN - 0023-6837
VL - 88
SP - 1329
EP - 1339
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 12
ER -