TY - JOUR
T1 - Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E
AU - Miller, Rachel L.
AU - Eppinger, Thomas M.
AU - McConnell, David
AU - Cunningham-Rundles, Charlotte
AU - Rothman, Paul
PY - 1998
Y1 - 1998
N2 - Background: Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors. The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6, whereas the inhibition of IgE class switching by interferon-γ (IFN-γ) occurs through the activation of Stat1. Objective: We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E [HIE]) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6. Methods: PBMCs and sera from 8 patients with extrinsic asthma (mean IgE, 285 ± 100 IU/mL), 3 patients with HIE (mean IgE, 7050 ± 1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112 ± 28 IU/mL) were analyzed. Results: The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects (88.6 ± 11.5 pg/mL vs 11.5 ± 7.1 pg/mL, P = .005), and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels. In contrast, IL-13 levels were not elevated. Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects. Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma. Interestingly, evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE. Conclusion: These results indicate that (1) IgE production in asthma and HIE usually is associated with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs; and (3) evidence of switch recombination to ε may be detected in isolated cases of elevated IgE. This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching, from Ig class switching that is localized to target tissues, or both.
AB - Background: Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors. The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6, whereas the inhibition of IgE class switching by interferon-γ (IFN-γ) occurs through the activation of Stat1. Objective: We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E [HIE]) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6. Methods: PBMCs and sera from 8 patients with extrinsic asthma (mean IgE, 285 ± 100 IU/mL), 3 patients with HIE (mean IgE, 7050 ± 1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112 ± 28 IU/mL) were analyzed. Results: The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects (88.6 ± 11.5 pg/mL vs 11.5 ± 7.1 pg/mL, P = .005), and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels. In contrast, IL-13 levels were not elevated. Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects. Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma. Interestingly, evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE. Conclusion: These results indicate that (1) IgE production in asthma and HIE usually is associated with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs; and (3) evidence of switch recombination to ε may be detected in isolated cases of elevated IgE. This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching, from Ig class switching that is localized to target tissues, or both.
KW - Extrinsic asthma
KW - Hyperimmunoglobulin E
KW - IL-13
KW - IL-4
KW - Stat6
KW - Switch recombination
UR - http://www.scopus.com/inward/record.url?scp=0031661071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031661071&partnerID=8YFLogxK
U2 - 10.1016/S0091-6749(98)70141-1
DO - 10.1016/S0091-6749(98)70141-1
M3 - Article
C2 - 9768594
AN - SCOPUS:0031661071
VL - 102
SP - 503
EP - 511
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -