White K L, Lysy H H, McCay J A, Anderson A C
Toxicol Appl Pharmacol. 1986 Jun 30;84(2):209-19. doi: 10.1016/0041-008x(86)90128-6.
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.
对雌性B6C3F1小鼠进行为期14天的2,3,7,8-四氯二苯并对二恶英（TCDD）亚慢性暴露，剂量为0.01、0.05、0.1、0.5、1.0和2.0微克/千克时，会抑制血清总溶血补体活性（CH50）。剂量为0.5、1.0和2.0微克/千克时，补体成分C3的血清水平也会受到抑制。另一种二恶英异构体，1,2,3,6,7,8-六氯二苯并对二恶英（HCDD），在剂量为0.1、1.0和10微克/千克时也会产生剂量依赖性的补体活性抑制，在10微克/千克时C3水平降低。TCDD和HCDD都会增强对肺炎链球菌的易感性，肺炎链球菌是一种宿主防御由补体介导的细菌病原体。恢复研究表明，经TCDD（1微克/千克）和HCDD（10微克/千克）处理的动物的补体活性在处理后50天内一直受到抑制，而低剂量的HCDD（0.1和1.0微克/千克）会提高CH50水平。急性暴露于TCDD（14微克/千克）也会抑制补体CH50和C3水平。这些研究表明，补体系统和固有免疫是多氯二苯并对二恶英的潜在靶位点。
