Orally administered lead chloride induces bias of mucosal immunity.
The hypothesis that lead disturbs gut immune functions upon oral ingestion was tested. Long-term exposure to oral PbCl(2)for 10 days caused persistent downregulation of TGF-beta mRNA levels in intestinal tissue. PbCl(2) also disturbed oral tolerance induction to the dietary antigen ovalbumin. Upon challenge with an immunizing dose of ovalbumin and rechallenge of draining lymph node cells in vitro, tolerance induction was partially suppressed in animals exposed to oral PbCl(2). This was shown by increased proliferation to antigenic stimulus, increased production of IFN-gamma and decreased secretion of TGF-beta. In conclusion, we show for the first time that oral exposure to PbCl(2)has a significant effect on the gut immune system, demonstrated by a bias of the cytokine pattern towards Th(1)and by disturbed oral tolerance mechanisms.
Goebel
C
C
German Diabetes Research Institute, Heinrich-Heine-University Düsseldorf, Germany.
Flohé
S B
SB
Kirchhoff
K
K
Herder
C
C
Kolb
H
H
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007109:Immunity / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000008:administration & dosage* / Q000494:pharmacology*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D007854:Lead; C029891:lead chloride; D007371:Interferon-gamma; D010047:Ovalbumin