Dual effects of vitamin D–induced alteration of TH1/TH2 cytokine expression  Victor Matheu, MD, Ove Bäck, MD, PhD, Emma Mondoc, BSc, Shohreh Issazadeh-Navikas,

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Dual effects of vitamin D–induced alteration of TH1/TH2 cytokine expression  Victor Matheu, MD, Ove Bäck, MD, PhD, Emma Mondoc, BSc, Shohreh Issazadeh-Navikas, PhD  Journal of Allergy and Clinical Immunology  Volume 112, Issue 3, Pages 585-592 (September 2003) DOI: 10.1016/S0091-6749(03)01855-4

FIG 1 In vitro response in cultured splenocytes. A, No difference between control (□) and vitamin D–treated (■) mice after unspecific stimulation was seen. However, there was an increase in OVA-specific response in the vitamin D–treated group. B, Proliferation was suppressed by means of in vitro addition of vitamin D in both vitamin D–treated (■) and control (□) mice. C, OVA-specific cytokine production by spleen cells in vitamin D–treated (■) and control (□) mice is shown. IL-5 levels were significantly decreased in vitamin D–treated mice. Histograms show values expressed as means ± SEM (n = 6 mice per group). ∗P < .05. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 2 Serum levels of OVA-specific IgE (A) and IgG1 (B) in control (□) and vitamin D–treated (■) mice determined by means of ELISA. Histograms show values expressed as means ± SEM in picograms per milliliter. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 3 Cytokine levels in BAL fluid determined by means of ELISA in control (□) and vitamin D–treated (■) mice. IFN-γ levels were undetectable. Histograms show values expressed as means ± SEM in picograms per milliliter. ∗P < .05. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 4 A, Eosinophils in BAL fluid and lung samples were decreased in vitamin D–treated (■) compared with control (□) mice. B, Eosinophils, with their characteristic brown color, are observed in a collapsed airway with a mucus plug from a control mouse. C, Few eosinophils are seen in a vitamin D–treated mouse. D, Percentages and total numbers of eosinophils in IL-4−/− mice were decreased in vitamin D–treated mice. The number of affected airways with a presence of airway epithelial mucus cells was also diminished after treatment with vitamin D. Percentages and total numbers of eosinophils in airways of IL-4−/− mice were decreased in vitamin D–treated mice. Histogram shows values expressed as means ± SEM. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 4 A, Eosinophils in BAL fluid and lung samples were decreased in vitamin D–treated (■) compared with control (□) mice. B, Eosinophils, with their characteristic brown color, are observed in a collapsed airway with a mucus plug from a control mouse. C, Few eosinophils are seen in a vitamin D–treated mouse. D, Percentages and total numbers of eosinophils in IL-4−/− mice were decreased in vitamin D–treated mice. The number of affected airways with a presence of airway epithelial mucus cells was also diminished after treatment with vitamin D. Percentages and total numbers of eosinophils in airways of IL-4−/− mice were decreased in vitamin D–treated mice. Histogram shows values expressed as means ± SEM. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 4 A, Eosinophils in BAL fluid and lung samples were decreased in vitamin D–treated (■) compared with control (□) mice. B, Eosinophils, with their characteristic brown color, are observed in a collapsed airway with a mucus plug from a control mouse. C, Few eosinophils are seen in a vitamin D–treated mouse. D, Percentages and total numbers of eosinophils in IL-4−/− mice were decreased in vitamin D–treated mice. The number of affected airways with a presence of airway epithelial mucus cells was also diminished after treatment with vitamin D. Percentages and total numbers of eosinophils in airways of IL-4−/− mice were decreased in vitamin D–treated mice. Histogram shows values expressed as means ± SEM. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 4 A, Eosinophils in BAL fluid and lung samples were decreased in vitamin D–treated (■) compared with control (□) mice. B, Eosinophils, with their characteristic brown color, are observed in a collapsed airway with a mucus plug from a control mouse. C, Few eosinophils are seen in a vitamin D–treated mouse. D, Percentages and total numbers of eosinophils in IL-4−/− mice were decreased in vitamin D–treated mice. The number of affected airways with a presence of airway epithelial mucus cells was also diminished after treatment with vitamin D. Percentages and total numbers of eosinophils in airways of IL-4−/− mice were decreased in vitamin D–treated mice. Histogram shows values expressed as means ± SEM. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)

FIG 5 Time table for vitamin D's effects. A, IgE levels are increased in all groups treated with vitamin D. B, IgG1 is decreased in all groups receiving early vitamin D treatment at sensitization from day −1 to day 3. C, Vitamin D downregulates eosinophilia as a late-stage effect when given at challenge from day 5 to day 9. ∗P < .05. Journal of Allergy and Clinical Immunology 2003 112, 585-592DOI: (10.1016/S0091-6749(03)01855-4)