Dietary phytosterols modulate T-helper immune response but do not induce apparent anti-inflammatory effects in a mouse model of acute, aseptic inflammation.
Although most studies have focused on the cholesterol-lowering activity of phytosterols, other biological actions have been ascribed to these plant sterol compounds, one of which is a potential immune modulatory effect. To gain insight into this issue, we used a mouse model of acute, aseptic inflammation induced by a single subcutaneous turpentine injection. Hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mice, fed with or without a 2% phytosterol supplement, were treated with turpentine or saline and euthanized 48 h later. No differences were observed in spleen lymphocyte subsets between phytosterol- and control-fed apoE(-/-) mice. However, cultured spleen lymphocytes of apoE(-/-) mice fed with phytosterols and treated with turpentine showed increased IL-2 and IFN-gamma secretion (T-helper type1, Th1 lymphocyte cytokines) compared with turpentine-treated, control-fed animals. In contrast, there was no change in Th2 cytokines IL-4 and IL-10. Phytosterols also inhibit intestinal cholesterol absorption in wild-type C57BL/6J mice but, in this case, without decreasing plasma cholesterol. Spleen lymphocytes of turpentine-treated C57BL/6J mice fed with phytosterols also showed increased IL-2 production, but IFN-gamma, IL-4 and IL-10 production was unchanged. The Th1/Th2 ratio was significantly increased both in phytosterol-fed apoE(-/-) and C57BL/6J mice. We conclude that phytosterols modulate the T-helper immune response in vivo, in part independently of their hypocholesterolemic effect in a setting of acute, aseptic inflammation. Further study of phytosterol effects on immune-based diseases characterized by an exacerbated Th2 response is thus of interest.
Calpe-Berdiel
Laura
L
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, 08025, Barcelona, Spain.
Escolà-Gil
Joan Carles
JC
Benítez
Sonia
S
Bancells
Cristina
C
González-Sastre
Francesc
F
Palomer
Xavier
X
Blanco-Vaca
Francisco
F
D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D019587:Dietary Supplements; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007111:Immunity, Cellular / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010840:Phytosterols / Q000494:pharmacology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D014425:Turpentine / Q000633:toxicity
D001057:Apolipoproteins E; D007376:Interleukin-2; D010840:Phytosterols; D007371:Interferon-gamma; D002784:Cholesterol; D014425:Turpentine