Assessment of host resistance to Trichinella spiralis in mice following preinfection exposure to 2,3,7,8-TCDD.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been reported to decrease host resistance to a variety of infectious agents when exposure occurs prior to infection. Resistance to viral infection has been observed at doses as low as 0.1 microgram TCDD/kg body wt, well below the thymolytic dose in mice. In the present study, female B6C3F1 mice were exposed to a single intraperitoneal injection of 0, 0.1, 1.0, 10.0, or 30.0 micrograms TCDD/kg 7 days prior to infection to determine the effects of TCDD exposure on resistance to the nematode parasite Trichinella spiralis. Exposure to 10 or 30 micrograms TCDD/kg delayed adult parasite elimination from the small intestine. Significantly more larvae were released by female parasites and greater numbers of encysted larvae were recovered from the muscle of mice exposed to TCDD. Proliferative responses of splenocytes and mesenteric lymph node cells stimulated with T. spiralis antigen were significantly suppressed at exposure levels of TCDD > or = 1.0 microgram/kg 7 days after infection and in splenocytes only at 14 days after infection, demonstrating the greater sensitivity of proliferative responses to TCDD exposure than actual host resistance to Ts infection. Suppressed proliferation was observed at doses which produced TCDD concentrations > or = 0.2 pmol/g of lymphoid tissue on Day 7 of infection. In addition, it was determined that infected mice had higher TCDD levels than noninfected mice given the same dose. These results suggest an interaction between TCDD exposure and infection, i.e., that exposure to TCDD altered the host response to infection, while infection delayed elimination of TCDD from the host.
Luebke
R W
RW
Environmental Toxicology Division, U.S. EPA, Research Triangle Park, North Carolina 27711.
Copeland
C B
CB
Diliberto
J J
JJ
Akubue
P I
PI
Andrews
D L
DL
Riddle
M M
MM
Williams
W C
WC
Birnbaum
L S
LS
D000704:Analysis of Variance; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006790:Host-Parasite Interactions / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007421:Intestine, Small / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D017160:Trichinella spiralis / Q000276:immunology* / Q000302:isolation & purification; D014235:Trichinellosis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology
D000947:Antigens, Helminth; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System