The gut cytokine balance as a target of lead toxicity.
The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. Oral tolerization with ovalbumin (OVA) increased levels of IL-10 and TGF-beta in gut tissue while IFN-gamma mRNA levels remained unchanged in both autoimmune diabetes prone NOD and normal C57BL/6 mice. This shift towards Th2/Th3 type cytokine gene expression was completely abolished by concomitant treatment with PbCl2 (6 x 0.5 mg/kg) in NOD mice while the cytokine balance in C57BL/6 mice was unaffected. Suppression of Th2/Th3 type cytokine expression was associated with a dampened oral tolerance response to OVA as determined by T cell proliferation assays. We conclude that in autoimmunity prone NOD mice environmental toxicants may disturb immune homeostasis by targeting the gut immune system.
Goebel
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C
Diabetes Research Institute, Heinrich-Heine-University Düsseldorf, Germany. goebel@dfi.uni.duesseldorf.de
Kirchhoff
K
K
Wasmuth
H
H
Flohé
S
S
Elliott
R B
RB
Kolb
H
H
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D016207:Cytokines / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics
D000941:Antigens; D016207:Cytokines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007854:Lead; D010047:Ovalbumin