An immunotoxicological evaluation of 4,4'-thiobis-(6-t-butyl-m-cresol) in female B6C3F1 mice. 2. Humoral and cell-mediated immunity, macrophage function, and host resistance.
Adult female B6C3F1 mice were gavaged with TBBC in corn oil at doses of 10, 100, or 200 mg/kg daily for 14 consecutive days. All immunological parameters were measured 24 hr after the last chemical exposure. When indicated, animals were immunized during the exposure. TBBC produced a decrease in the peak IgM (44%) and peak IgG (48%) antibody response to sheep erythrocytes (SRBCs), but had no effect on the delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH). Paradoxically, TBBC caused an overall increase in the number of splenic cells, a decrease in the percentage of splenic T cells and no effect on the percentage of splenic B cells. There were no effects on the lymphoproliferative responses to optimal concentrations of concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS), but there was a significant decrease in the mixed lymphocyte response (MLR). In both the mitogen assays and the MLR there was a dose-related increase in the basal (unstimulated) DNA synthesis of the spleen cells. Innate immunity, as measured by natural killer (NK) cell activity and serum complement, was significantly increased. Effects on macrophage function were complex, as an increase or no effect was observed depending on the parameter measured. In the host resistance models, animals were infected with various pathogens 24 hr after the last chemical exposure. Exposure to TBBC caused an increased resistance to challenge with Streptococcus and B16F10 melanoma, a decreased resistance to challenge with PYB6 tumors, and no effect on the resistance to HSV-2, Listeria or Plasmodium.
Holsapple
M P
MP
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
White
K L
KL
McCay
J A
JA
Bradley
S G
SG
Munson
A E
AE
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D003165:Complement System Proteins / Q000276:immunology; D003408:Cresols / Q000633:toxicity*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis / Q000187:drug effects
D003408:Cresols; D003165:Complement System Proteins; C040020:4,4'-thiobis(6-tert-butyl-3-cresol)