Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model.
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.
Adapala
Nagasuresh
N
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Chan
Marion M
MM
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
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047495:PPAR gamma; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin
Annu Rev Immunol. 1997;15:323-50
9143691
Planta Med. 2006 Aug;72(10):881-7
16858665
Biol Pharm Bull. 2002 Mar;25(3):386-9
11913540
Parasite Immunol. 1985 Sep;7(5):545-55
3877902
Cancer Lett. 1995 Sep 4;96(1):23-9
7553604
Biochem Biophys Res Commun. 1995 Jan 17;206(2):533-40
7530002
Am J Epidemiol. 2004 Aug 15;160(4):339-49
15286019
Biochem Pharmacol. 1995 May 26;49(11):1551-6
7786295
Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):85-98
8118391
J Immunol. 1990 Dec 15;145(12):4290-7
2124240
Trans R Soc Trop Med Hyg. 2001 Apr;95 Suppl 1:S27-58
11370250
Crit Care Med. 2006 Jul;34(7):1874-82
16715036
J Clin Microbiol. 2002 May;40(5):1666-9
11980939
Life Sci. 2006 Mar 27;78(18):2026-32
16497339
Microb Pathog. 2005 Apr;38(4):147-60
15797810
Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1542-8
15166011
Biochem Pharmacol. 1998 Jun 15;55(12):1955-62
9714315
Annu Rev Immunol. 1995;13:151-77
7612219
Clin Rheumatol. 2007 Aug;26(8):1344-5
16865310
Am J Physiol Gastrointest Liver Physiol. 2005 Mar;288(3):G447-56
15486348
Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G113-23
16959952
Trends Parasitol. 2004 Nov;20(11):524-30
15471704
Biochem Pharmacol. 2004 Jul 1;68(1):51-61
15183117
J Intensive Care Med. 2004 Nov-Dec;19(6):320-34
15523118
Nutr Rev. 1996 Nov;54(11 Pt 2):S127-31
9110589
Br J Pharmacol. 1999 Sep;128(2):380-4
10510448
Parasitol Res. 2005 Apr;96(1):49-56
15772867
J Exp Med. 1989 Jan 1;169(1):59-72
2521244
Infect Immun. 2002 Nov;70(11):6284-93
12379707
Nature. 1999 Jul 22;400(6742):378-82
10432118
Nat Rev Immunol. 2004 Nov;4(11):912-21
15516970
J Immunol. 1990 Dec 15;145(12):4306-10
2175327
Anticancer Res. 2001 Jul-Aug;21(4B):2895-900
11712783
Res Immunol. 1995 Sep-Oct;146(7-8):423-31
8839141
J Exp Med. 1999 Feb 15;189(4):741-6
9989990
Eur J Immunol. 2001 Oct;31(10):2848-56
11592059
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7
12740443
Natl Med J India. 1999 Mar-Apr;12(2):62-8
10416321