Chronic oral exposure to low-concentration fumonisin B2 significantly exacerbates the inflammatory responses of allergies in mice via inhibition of IL-10 release by regulatory T cells in gut-associated lymphoid tissue.

Contamination with fumonisins produced by Fusarium spp. is rapidly growing in both developing and developed countries. The purpose of this study was to determine whether oral exposure to fumonisin contributed to the development of allergic diseases. We initially examined the immunotoxic potential of short-term, oral administration of fumonisin B1 (FB1, 1 mg/kg) and fumonisin B2 (FB2, 1 mg/kg), both naturally occurring fumonisins, using a BALB/c mouse model of allergic contact dermatitis and Dermatophagoides farina-induced asthma. Using an NC/nga mouse model of atopic dermatitis (AD), we evaluated the adverse effects of subchronic oral exposure to low concentrations of FB2 (2 or 200 µg/kg). Finally, we explored the influence of FB2 on regulatory T cell proliferation and function in mesenteric lymph nodes after 1-week oral exposure to FB2 in BALB/c mice. Oral exposure to FB2 markedly exacerbated the symptoms of allergy, including skin thickness, histological evaluation, immunocyte proliferation, and proinflammatory cytokine production, although no change was observed following exposure to FB1. Furthermore, oral exposure to low concentrations of FB2 considerably exacerbated the AD scores, skin thickness, transepidermal water loss, histological features, and proinflammatory cytokine production. The aggravated allergic symptoms induced by oral exposure to FB2 could be attributed to the direct inhibition of IL-10 production by regulatory T cells in mesenteric lymph nodes. Our findings indicate that the recommended maximum fumonisin level should be reconsidered based on the potential for allergy development.

Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis.

Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.

Acute and Subacute Oral Toxicity of Deoxynivalenol Exposure in a Dermatophagoides farinae-Induced Murine Asthma Model.

Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1ß, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.

Collective Psychology and Behavioral Characteristics of Patients with Inflammatory Bowel Disease: A Single Cohort Study.

BACKGROUND: We previously treated patients with inflammatory bowel disease (IBD) using color therapy as part of projective psychotherapy and found differences in preferred colors selected in an imagined stressful situation between patients with ulcerative colitis (UC) and those with Crohn's disease (CD). In this study, we investigated differences in color selection among UC patients, CD patients, and healthy volunteers (HVs). More precisely, formal analysis using a projective technique was performed to evaluate their emotional characteristics when coping with stress, and egogram analysis was performed to investigate their collective psychological characteristics and behavioral characteristics as social selves. METHODS: Eighty-three HVs, 70 UC patients, and 71 CD patients were shown a sheet displaying images of bottles each containing 2 horizontally separated compartments filled in the same color or different colors. The preferred colors selected under imagined psychological stress (loneliness) were analyzed using a projection approach to investigate the emotional characteristics of the inner self. The Tokyo University Egogram New Version II (TEG®II) was then used to analyze collective psychological characteristics and behavioral characteristics as social selves in the HV, UC, and CD groups. RESULTS: Comparison of all 3 groups with the χ2 test showed that more participants chose calm colors in the CD group than in the HV and UC groups, while more participants chose stimulating colors in the UC group than in the CD group (p < 0.01). Analysis of TEG®II results with one-way analysis of variance and then with the Tukey-Kramer multiple comparison test revealed differences in collective psychological characteristics and behavioral characteristics in all 3 groups. Comparing scores for 5 types of ego states (Critical Parent, Nurturing Parent, Adult, Free Child, and Adapted Child) revealed that more participants in the CD group had a low Critical Parent score than in the HV group (p < 0.05). More participants in the IBD group had a low Nurturing Parent score than in the HV group (CD vs. HV, p < 0.01; UC vs. HV, p < 0.05). Significantly more participants in the UC group had a higher Adult score than in the HV or CD group (each p < 0.01). CONCLUSIONS: The psychological characteristics of patients with IBD differ depending on the type of disease (i.e., CD vs. UC). Management based on such differences should be provided for patients with each disease type.