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NK and Immune Suppression by Aflatoxins?

Discussion in 'Other Research' started by Not dead yet!, Apr 12, 2018.

  1. Not dead yet!

    Not dead yet! Well-Known Member

    There's an interesting article I read recently about aflatoxins. I'm wondering if this may be the driving force of all the "no grains, no legumes" movements? If so, then it should include "no nuts" too. What's really interesting is, the toxins can build up in animals and be passed on in the milk and meat. Could explain so much about random illness after eating. And it causes lethargy... hmm. I'll add the part about immune suppression... even NK cell effects. Double hmm... I wonder what the cytokines look like.


    Article: Immunologic suppression

    As stated earlier, most of the information summarized below is derived from studies of farm animals or from animal models in which the exposure is chronic but not high enough to cause the symptoms usually associated with acute aflatoxicosis. Human exposure is likely to be more variable than that in these studies, because of the highly variable distribution of contamination within foods. Aflatoxin M1 (AFM1) in human urine reflects exposure over the previous 24 h and is usually found in approximately one-third of the members of a sample population, whereas aflatoxin-albumin adduct data, which reflect exposure over a longer period, are present in most (>90%) of the same populations (24, 28, 29). This difference provides some uncertainty about the extension of animal data to humans, but some publications show that these animal responses are relevant to humans, at least in broad terms. The threshold dose for immunotoxic effects in humans is not known.

    In animal experiments, AFB1 has been shown to induce thymic aplasia (30), reduce T-lymphocyte function and number, suppress phagocytic activity, and reduce complement activity (30–32). Many studies conducted in poultry, pigs, and rats showed that exposure to aflatoxin in contaminated food results in suppression of the cell-mediated immune responses (17, 33–37). Thymic and bursal involution, suppression of lymphoblastogenesis, impairment of delayed cutaneous hypersensitivity (37, 38), and graft-versus-host reaction (39, 40) also occur in animals exposed to aflatoxin. Splenic CD4 (helper T) cell numbers and interleukin 2 (IL-2) production decreased significantly when mice were treated with AFB1 at a dose of 0.75 mg/kg (41). Impairment of cellular function by aflatoxin seems to be due to its effects on such factors as the production of lymphokines and antigen processing by macrophages (42), as well as a decrease in or lack of the heat-stable serum factors involved in phagocytosis (43).

    Macrophages play a major role in host defenses against infection. They present antigen to lymphocytes during the development of specific immunity and serve as supportive accessory cells to lymphocytes. Macrophages also increase their phagocytic activity and release various active products, such as cytokines and reactive intermediates, to carry out nonspecific immune responses (44). Several reports suggest that aflatoxin impairs the function of macrophages in animal species (45, 46). In addition to its reported effect in reducing phagocytic activity in rabbit alveolar macrophages (43), aflatoxin has more recently been shown in vitro to inhibit phagocytic cell function in normal human peripheral blood monocytes (46). AFB1 at concentrations ≥100 pg/mL was cytotoxic to the monocytes, and concentrations of 0.5 to 1 pg/mL inhibited monocyte phagocytic activity and intracellular killing of Candida albicans; however, superoxide production and the ability of the monocytes to destroy intracellular herpes simplex virus were not affected.

    AFB1 given orally at concentrations of 0.03-0.07 mg/kg suppressed natural killer (NK) cell-mediated cytolysis of YAC-1 target cells in BALB/c mice (47), but not in C57B1/6 mice at the same dose (41) or in rabbits fed 24 ppm aflatoxin in feed (48). Pigs that received 500 ppm AFB1 in their feed had reduced total hemolytic serum complement activity (49), but complement activity was not affected in pigs fed 300 ppm or rabbits fed 95 ppm AFB1. These differences serve to show that the species differences, noted for acute toxicity and carcinogenicity, also apply to immune responses.

    Theumer et al (50) fed rats a diet containing 40 ppb AFB1 for 90 d. The mitogenic response of spleen mononuclear cells (SMNCs) in vivo was higher in animals fed with AFB1 than in those not so fed. The SMNCs of animals fed with AFB1 produced lower concentrations of IL-2, higher concentrations of IL-4, and equal amounts of IL-10.

    Marin et al (51) conducted studies to evaluate the humoral and cellular immune responses in weaning piglets (x̄ ± SD body weight: 11.42 ± 0.11 kg) exposed to 140 and 280 ppb aflatoxin for 4 wk. Humoral and cellular immune functions were impaired, and aflatoxin reduced the primary and the secondary immune response. Antibody levels from immunization to Mycoplasmaagalactiae (an infectious microorganism) were always lower in aflatoxin-fed animals than in control piglets.

    The immunosuppressive effects of aflatoxin were also shown to be transferred across the porcine placenta and to affect the unborn fetus (17). Pigs born to sows fed aflatoxin and sensitized with Mycobacterium tuberculosis had a smaller delayed cutaneous hypersensitivity reaction than did pigs who were not exposed to aflatoxin or sensitized with M tuberculosis. Cell-mediated and phagocytic functions and, to a lesser extent, humoral immune function have also been shown to be reduced in the offspring of pigs and rats exposed to aflatoxin in their diets (17, 36, 52). Moreover, chick embryos exposed to a single 0.1-mg dose of AFB1 had a depressed graft-versus-host response and a depressed cutaneous basophil hypersensitivity to injected phytohemagluttin (39). In rainbow trout, long-term effects on immune system functions were shown to result from exposure of the ova to aflatoxin (53).

    Given the effect of aflatoxin on the immune system, it is not surprising that there is evidence that the value of vaccination is modified by exposure to aflatoxin. Significantly, aflatoxin exposure was also shown to reduce the antibody response to vaccines. Studies conducted in poultry showed that daily dietary exposure through foods with aflatoxin concentrations of 200 ppb for ≤40 wk reduced antibody titers to vaccines for Newcastle disease, infectious bronchitis, and infectious bursal disease (54, 55). In rabbits, aflatoxin was also found to reduce antibody titers to Mycobacteriumbovis (56), Bordetellabronchiseptica (57), and Pasteurellamultocida (58). Decreased effectiveness of vaccination against swine fever (59), hemorrhagic septicemia (60), and foot and mouth disease (DK Singh, personal communication, 1997) in dairy cattle has also been observed.

    As previously indicated, evidence for in vivo immunosupression by aflatoxin in humans is limited, inconsistent, and uncertain. The available studies of human exposure usually measured the aflatoxin-albumin adduct concentration, which reflects long-term exposure. Given the toxicology of aflatoxin and the recovery of cell processes within days of exposure (61), aflatoxin- albumin adduct may not always be an appropriate measure of exposure for immune function changes. Turner et al (62) did observe changes in immunity in Gambian children as a function of aflatoxin-albumin adducts, which were detected in 93% of the children (geometric x̄: 22.3 pg/mg; range: 5-456 pg/mg). The aflatoxin-albumin adduct concentration was strongly influenced by the month of sampling. In a multivariable analysis, secretory immunoglobulin A (IgA) was markedly lower in children with detectable aflatoxin-albumin concentrations than in those with nondetectable concentrations. Furthermore, a weak antibody response to a pneumococcal challenge was observed, but the response to rabies vaccine and cell-mediated immunity responses to test antigens were not related to adduct status. In an earlier study, also in the Gambia, Allen et al (27) observed that there was no obvious relation between aflatoxin-albumin concentrations and malaria-specific antibody responses or in vitro lymphoproliferative responses. However, using the mouse-Plasmodium berghei model, Young et al (63) found that aflatoxin decreased morbidity because of a direct effect of aflatoxin on the parasite.

    Our unpublished data (manuscript in preparation) show significant suppression of select cellular immune system components and functions when Ghanaian subjects with aflatoxin-albumin adduct concentrations above the median (0.80 pmol/mg) for the population were compared with those with concentrations below the median.
    Merry likes this.