Does systemic exposure to aflatoxin B1 cause allergic sensitization?


Can Naci Kocabaş, MD Department of Pediatric Allergy and Astma Faculty of Medicine Hacettepe University 06100 Sihhiye, Ankara Turkey


The worldwide increasing prevalence of allergic diseases over the last two decades, together with the fact that the prevalence of such diseases has become more notable in more developed than less developed countries, is a strong indication that environmental factors are of great significance in the development of allergic diseases. Some environmental factors (Endotoxins, BCG vaccination, Rubella and Hepatitis A infections, feeding with probiotics, etc.), as suggested in the hygiene hypothesis, may prevent the development of atopic diseases (1–5).

People, especially living in less developed countries, are frequently exposed to aflatoxins through food ingestion (6, 7). Aflatoxins are highly oxygenated, heterocyclic compounds produced by some strains of Aspergillus flavus and A. parasiticus. Four major structurally related aflatoxins have been identified which designated as B1, B2, G1 or G2. However, aflatoxin B1 (AFB1) is the primary form, and the majority of health effect studies have focused on it. Aspergillus species which produce aflatoxin B1 have a particular affinity for nuts, oilseeds and cereals (8, 9). Primarily, inadequate drying or improper storage of foods are certainly important in the occurrence of aflatoxins in the humidity of the tropics (9, 10). In contrast, in more developed countries, stringent sorting and clean up procedures are used to reduce aflatoxins to low levels in foods, but in spite of this, aflatoxin ingestion remains far too high, even in many developed countries, especially in rural areas (9, 11). In addition, aflatoxins are also found in significant amounts in respirable particles of grain dust and are an occupational health hazard when people are exposed to it (12–14). In utero exposure of AFB1 to both animals and humans has been reported and its exposure to developing individuals may take place through ingestion of mother's milk (14,15). The presence of AFB1 has also been reported in marketed milk samples from several countries (16). The contaminated milk is often consumed by growing individuals both in developed and developing countries. A growing individual exposed to AFB1 under such situations may be more susceptible to its toxicity compared with an adult. Aflatoxin B1 have been reported to impair the immune functions, including production of antibodies, cell-mediated responses and natural killer activity (17–19). It has been reported that AFB1 has a selective effect on cell-mediated immunity with a relatively minor effect on the humoral immune system (17). These reports indicate that the most probable mechanism of AFB1-induced cell-mediated immunosuppression is likely to be the inhibition of interleukin-2 (IL-2) and interferon-γ (IFN-γ) production (17, 20). Thus, the decrease of the IFN-γ level plays a major role in the development of allergen sensitization during infancy, while the capacity of T helper (Th) cells to secrete IFN-γ is markedly reduced in neonates (21–23). For this reason, we suggest that the reduced neonatal IFN-γ producing capacity would be even more pronounced in infants that were exposed to AFB1 especially during the infancy period and so there is a tendency to develop allergic sensitization. Moreover, it has been indicated that TNF-α and IL-1α, which play a role in the development of cell-mediated immunity by generating IL-2 and IL-12, are inhibited by AFB1 (18, 24). For instance, AFB1 can affect cell-mediated immunity by inhibiting these cytokines resulting in an inhibition of signals activating Th1 cells to respond to foreign antigens. Atopic diseases are developed as a result of the conversion of naive Th cells to Th2 instead of Th1 (21). When exposure to AFB1 occurs during the first years of life, inhibited Th1 immune response may stimulate the balance of Th1/Th2 skew toward Th2 immune response.

T helper 1 cells protect against asthma and allergy and can reverse the effects of Th2 driven inflammation. The beneficial role of the Th1 cells in allergic disease is supported by studies that CD8+ T cells secreting enhanced amounts of IFN-γ maintain homeostasis after allergen inhalation (25). Additionally, the level of IFN-γ appears to contribute to the severity of the disease (26).

In conclusion, this issue is one of the major health problems faced by people, especially those living in less developed countries. As AFB1 is excreted in both mother's milk and cow's milk, which are consumed widely by infants, it is a significant problem (14, 16). Because of their high toxicity, low limits for aflatoxins in foods and feeds have been set by many countries. According to recent agreements, 15 μg/kg of total AFB1 is likely to become the maximum level permitted in all world-traded food commodities (9).

It is noteworthy that in Africa, asthma is often seasonal and 90% of asthmatic patients were skin test positive to house dust mite (27, 28). We speculated that this may be the result of the ideal conditions for mite and also aspergillus molds growth during wet season in tropical countries when a high relative humidity occurs. In contrast, people who live in rural areas of Africa are more exposed to AFB1 and yet display a lower prevalence of atopic diseases when compared with western population. We thought that because of being immunosuppressive, a secondary AFB1 may increase bacterial, viral and parasitic infections, and subsequently Th1 immune response may be stimulated. Although we possess a reasonable knowledge, further study is necessary to understand the effects of aflatoxin on atopic diseases.