Serum-borne factor(s) of 1,1-dichloroethylene and 1,2-dichlorobenzene-treated mice inhibited in vitro antibody forming cell response and natural killer cell activity.
1,1-Dichloroethylene and 1,2-dichlorobenzene administered to mice produced liver and/or kidney damage which was quantified in this study by a histochemical method. The in vitro effect of sera obtained from these mice on antibody forming cell (AFC) response and natural killer (NK) cell activity was investigated in parallel with the assessment of sera tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. 1,1-Dichloroethylene (100, 150 and 200 mg/kg) provoked liver and kidney damage. Peak kidney damage occurred 16 h after the dose was administered and at 24 h in the case of the liver. During the peak level of liver damage, a serum-borne immunosuppressive effect was also at its highest level. With respect to sera cytokine levels, an increase of TNF-alpha and IL-6 was detected earlier, i.e. 6 h after toxic administration, followed by a decrease that tended toward a baseline level. There was a relationship between the tissue damage induced by 1,1-dichloroethylene and the immunosuppressive effect of mice sera on AFC response and NK cell activity. 1,2-Dichlorobenzene (300, 500 and 600 mg/kg) provoked only liver damage. Peak liver damage severity was observed 48 h after toxic administration, whereas the highest serum-borne immunosuppressive effect was observed almost immediately, i.e. 6 h after administration. As regards sera cytokine levels, only TNF-alpha could be detected 6 h after administering 500 and 600 mg/kg doses of 1,2 dichlorobenzene. There was a relationship between the liver damage induced by 1,2-dichlorobenzene and the immunosuppressive effect of mice sera on the AFC response. In view of the above results, this study suggests that the immunosuppressive effect in sera of mice treated with 1,1-dichloroethylene and 1,2-dichlorobenzene may result from tissue damage, and that the increased levels of TNF-alpha and IL-6 in sera may contribute to this effect. Further studies are needed to clarify the factor(s) responsible, including transforming growth factor-beta1 (TGF-beta1) causing immunosuppression.
Ban
M
M
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Hettich
D
D
Goutet
M
M
Binet
S
S
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002722:Chlorobenzenes / Q000276:immunology* / Q000633:toxicity; D004000:Dichloroethylenes / Q000276:immunology* / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000097:blood / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D002722:Chlorobenzenes; D004000:Dichloroethylenes; D015850:Interleukin-6; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C029297:vinylidene chloride; C004726:2-dichlorobenzene