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Carrageenan cytotoxicity and the primary immune response
ANTIOXIDANTS
1141
clearance studies were not carried out in this case, but separate experiments were undertaken to determine the effect of SAIB on BSP clearance both in rats fed 4 ~o in the diet for 7 days and in squirrel monkeys given a single dose of approximately 2 g/kg. In neither case was any effect detected.
2614. Carrageenan cytotoxicity and the primary immune response
Bice, D. E., Gruwell, D. G., Salvaggio, J. E. & Hoffmann, E. O. (1972). Suppression of primary immunization by carrageenan--a macrophage toxic agent. Immun. Commun. 1, 615. Among the biological effects of carrageenan (Cited in F.C.T. 1971, 9, 561) is an ability to interfere with various aspects of the immune response. It has been shown to inhibit the C'1 component of complement (Davies, Immunology 1965, 8, 291), to interfere with the establishment of delayed hypersensitivity reactions (Bice et al. Int. Archs Allergy appl. Immun. 1971, 41, 628) and to inhibit the progress of already established hypersensitivity reactions (Cited in F.C.T. 1972, 10, 260). Carrageenan-has also been shown to inhibit stimulation of lymphocytes by antigens that need to be processed by macrophages (Lake et al. J. Immun. 1971, 107, 1745), although it has no effect on lymphocyte stimulation that is not macrophage-dependent. Further light has now been shed on the mechanism by which carrageenan interferes with the immune response. When red blood cells from sheep are injected into mice by the ip or iv route, a serum antibody is formed. However, when mice undergoing a 5-day course of ip carrageenan injections were injected ip with sheep red blood cells on day 4, little or no antibody was elicited. Injection of large doses of carrageenan iv also suppressed the immune response to sheep red blood cells injected ip, but when the antigen was injected iv into the mice given carrageenan by the ip route, a normal antibody response occurred. The toxicity of carrageenan to macrophages has been established in vitro (Cited in F.C.T. 1972, 10, 260), and the suppression of the immune response demonstrated in this study is thought to be a direct result of the cytotoxic effect of carrageenan on the macrophages.
ANTIOXIDANTS 2615. Two more BHT metabolites
Shaw, Y.-S. & Chen, C. (1972). Ring hydroxylation of di-t-butylhydroxytoluene by rat liver microsomal preparations. Biochem. J. 128, 1285. In the rat the main metabolite of butylated hydroxytoluene (BHT) is BHT-acid, formed by way of the alcohol and aldehyde (Cited in F.C.T. 1968, 6, 533; ibid, 1971, 9, 906). Conversion to the alcohol is under the control of a liver microsomal enzyme, BHT oxidase (Gilbert & Golberg, Fd Cosmet. Toxicol. 1967, 5, 481). The metabolites BHT-dimer and BHT-dimer-quinone have also been identified (Cited in F.C.T. 1971, 9, 906; Akagi & Aoki, Chem. Pharm. Bull., Tokyo 1962, 10, 101), and the present paper reports that the rat microsomal enzymes are capable of converting BHT into two further compounds by means of ring hydroxylation. F.C.T. 11[6---0
1141
clearance studies were not carried out in this case, but separate experiments were undertaken to determine the effect of SAIB on BSP clearance both in rats fed 4 ~o in the diet for 7 days and in squirrel monkeys given a single dose of approximately 2 g/kg. In neither case was any effect detected.
2614. Carrageenan cytotoxicity and the primary immune response
Bice, D. E., Gruwell, D. G., Salvaggio, J. E. & Hoffmann, E. O. (1972). Suppression of primary immunization by carrageenan--a macrophage toxic agent. Immun. Commun. 1, 615. Among the biological effects of carrageenan (Cited in F.C.T. 1971, 9, 561) is an ability to interfere with various aspects of the immune response. It has been shown to inhibit the C'1 component of complement (Davies, Immunology 1965, 8, 291), to interfere with the establishment of delayed hypersensitivity reactions (Bice et al. Int. Archs Allergy appl. Immun. 1971, 41, 628) and to inhibit the progress of already established hypersensitivity reactions (Cited in F.C.T. 1972, 10, 260). Carrageenan-has also been shown to inhibit stimulation of lymphocytes by antigens that need to be processed by macrophages (Lake et al. J. Immun. 1971, 107, 1745), although it has no effect on lymphocyte stimulation that is not macrophage-dependent. Further light has now been shed on the mechanism by which carrageenan interferes with the immune response. When red blood cells from sheep are injected into mice by the ip or iv route, a serum antibody is formed. However, when mice undergoing a 5-day course of ip carrageenan injections were injected ip with sheep red blood cells on day 4, little or no antibody was elicited. Injection of large doses of carrageenan iv also suppressed the immune response to sheep red blood cells injected ip, but when the antigen was injected iv into the mice given carrageenan by the ip route, a normal antibody response occurred. The toxicity of carrageenan to macrophages has been established in vitro (Cited in F.C.T. 1972, 10, 260), and the suppression of the immune response demonstrated in this study is thought to be a direct result of the cytotoxic effect of carrageenan on the macrophages.
ANTIOXIDANTS 2615. Two more BHT metabolites
Shaw, Y.-S. & Chen, C. (1972). Ring hydroxylation of di-t-butylhydroxytoluene by rat liver microsomal preparations. Biochem. J. 128, 1285. In the rat the main metabolite of butylated hydroxytoluene (BHT) is BHT-acid, formed by way of the alcohol and aldehyde (Cited in F.C.T. 1968, 6, 533; ibid, 1971, 9, 906). Conversion to the alcohol is under the control of a liver microsomal enzyme, BHT oxidase (Gilbert & Golberg, Fd Cosmet. Toxicol. 1967, 5, 481). The metabolites BHT-dimer and BHT-dimer-quinone have also been identified (Cited in F.C.T. 1971, 9, 906; Akagi & Aoki, Chem. Pharm. Bull., Tokyo 1962, 10, 101), and the present paper reports that the rat microsomal enzymes are capable of converting BHT into two further compounds by means of ring hydroxylation. F.C.T. 11[6---0