The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
Identifieur interne : 000160 ( Ncbi/Curation ); précédent : 000159; suivant : 000161The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
Auteurs : Nasr Ya Hemdan [Allemagne, Égypte]Source :
- Journal of Occupational Medicine and Toxicology (London, England) [ 1745-6673 ] ; 2008.
Abstract
Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation.
Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed
Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios
It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.
Url:
DOI: 10.1186/1745-6673-3-25
PubMed: 18990205
PubMed Central: 2585571
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<author><name sortKey="Hemdan, Nasr Ya" sort="Hemdan, Nasr Ya" uniqKey="Hemdan N" first="Nasr Ya" last="Hemdan">Nasr Ya Hemdan</name>
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<affiliation wicri:level="1"><nlm:aff id="I2">Institute of Clinical Immunology and Transfusion Medicine – IKIT, Faculty of Medicine, University of Leipzig, Germany</nlm:aff>
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<affiliation wicri:level="1"><nlm:aff id="I3">Department of Zoology, Faculty of Science, University of Alexandria, Egypt</nlm:aff>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation.</p>
</sec>
<sec sec-type="methods"><title>Methods</title>
<p>Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed <italic>Salmonella enterica</italic>
, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. <italic>In vivo </italic>
experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored.</p>
</sec>
<sec><title>Results</title>
<p>Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios <italic>in vivo </italic>
correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals.</p>
</sec>
<sec><title>Conclusion</title>
<p>It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.</p>
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