Immunosuppressive effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) in the rat.
THI is a component of ammonia caramel, a widely used food colouring. The effect of THI on the immune system has been determined in the male F344 rat. THI was given in the drinking water at doses of 1, 10 and 50 mg/l (equivalent to 0.1, 1 and 5 mg/kg per day) to animals on a vitamin B6-deficient diet. After 1 week, the immune competence of the animals was assessed under continued THI treatment. No marked changes in thymus or spleen weight were observed after THI treatment, although there was an increased number of pyknotic cells in the thymic cortex, mainly engulfed by macrophages and there appeared to be a slight thinning of the cortex area. THI produced a significant loss in T and B lymphocytes in peripheral blood but not in the spleen. No change in natural killer (NK) cell activity against YAC-1 target cells was observed in the spleen. The observed increase in NK cell activity in peripheral blood was due to an increase in circulating large granular lymphocytes (LGL). Although the serum antibody titre against keyhole limpet haemocyanin (KLH) was not affected by THI treatment, B cells showed less proliferation when cultured with lipopolysaccharide. T cell function was impeded as measured in mitogen-induced proliferation assay, delayed-type hypersensitivity assay and host versus graft (popliteal lymph node) assay. The results indicate that THI is an immunosuppressor in the rat, in whom it can produce profound lymphopenia and suppression of cell-mediated immunity.
Gobin
S J
SJ
Department of Toxicology, St Bartholomew's Hospital Medical College, London, England, UK.
Phillips
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed; D007093:Imidazoles / Q000633:toxicity*; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D007093:Imidazoles; D007166:Immunosuppressive Agents; C049929:2-acetyl-4(5)-tetrahydroxybutylimidazole