Modulation of serum complement levels following exposure to polychlorinated dibenzo-p-dioxins.
Subchronic 14-day exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed serum total hemolytic complement activity (CH50) in female B6C3F1 mice at doses of 0.01, 0.05, 0.1, 0.5, 1.0, and 2.0 micrograms/kg. Serum levels of complement component C3 were also suppressed at doses of 0.5, 1.0, and 2.0 micrograms/kg. Another dioxin isomer, 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HCDD), also produced dose-dependent suppression of complement activity at doses of 0.1, 1.0, and 10 micrograms/kg with decreased C3 levels at 10 micrograms/kg. Both TCDD and HCDD enhanced susceptibility to Streptococcus pneumoniae, a bacterial pathogen whose host defense is complement mediated. Recovery studies demonstrated that complement activity in TCDD (1 microgram/kg) and HCDD (10 micrograms/kg)-treated animals was suppressed until 50 days post-treatment, while low doses of HCDD (0.1 and 1.0 micrograms/kg) elevated CH50 levels. Acute exposure to TCDD (14 micrograms/kg) also suppressed complement CH50 and C3 levels. These studies demonstrate that the complement system and innate immunity represent potential target sites for polychlorinated dibenzo-p-dioxins.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003179:Complement C3b / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D003180:Complement C3b Inactivator Proteins; D000072317:Polychlorinated Dibenzodioxins; D003179:Complement C3b; C046838:1,2,3,6,7,8-hexachlorodibenzodioxin