BACKGROUND: The atopic patient has a predisposition to selective synthesis of IgE antibodies to common environmental antigens. IgE production is upregulated by interleukin-4 (IL-4) and downregulated by interferon-gamma (IFN-gamma). IL-12 is a cytokine that induces IFN-gamma production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. METHODS: We examined IFN-gamma production in peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients. Moreover, sequences of the IL-12R beta(2) chain gene were analyzed. RESULTS: The serum IgE levels were negatively correlated (p < 0.001) with IFN-gamma production. In 24 out of 75 atopic patients, IFN-gamma production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-gamma production. Sequence analysis of the cDNA of IL-12R beta(2) revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-gamma production following IL-12 stimulation was under the detection limit. PBMCs cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine phosphorylation of Stat4. CONCLUSIONS: The results of our study indicate that atopic diseases are caused, in part, by impairment of the IL-12 signal cascade, which downregulates IgE production, and that the mutation of the IL-12R beta(2) chain gene is one of the causative genes for atopy. Copyright 2001 S. Karger AG, Basel
BACKGROUND: The atopic patient has a predisposition to selective synthesis of IgE antibodies to common environmental antigens. IgE production is upregulated by interleukin-4 (IL-4) and downregulated by interferon-gamma (IFN-gamma). IL-12 is a cytokine that induces IFN-gamma production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. METHODS: We examined IFN-gamma production in peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients. Moreover, sequences of the IL-12R beta(2) chain gene were analyzed. RESULTS: The serum IgE levels were negatively correlated (p < 0.001) with IFN-gamma production. In 24 out of 75 atopic patients, IFN-gamma production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-gamma production. Sequence analysis of the cDNA of IL-12R beta(2) revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-gamma production following IL-12 stimulation was under the detection limit. PBMCs cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine phosphorylation of Stat4. CONCLUSIONS: The results of our study indicate that atopic diseases are caused, in part, by impairment of the IL-12 signal cascade, which downregulates IgE production, and that the mutation of the IL-12R beta(2) chain gene is one of the causative genes for atopy. Copyright 2001 S. Karger AG, Basel
Authors: Eun Jin Kim; Won Mok Lee; Jung Sook Ha; Nam Hee Ryoo; Dong Suk Jeon; Jae Ryong Kim Journal: J Korean Med Sci Date: 2006-12 Impact factor: 2.153