TY - JOUR
T1 - Synergistic effects of interleukin 4 and interferongamma on monocyte phosphodiesterase activity
AU - Li, Shi Hua
AU - Chan, Sai C.
AU - Toshitani, Akito
AU - Leung, Donald Y.M.
AU - Hanifin, Jon M.
PY - 1992/7
Y1 - 1992/7
N2 - Patients with atopic dermatitis (AD) have elevated leukocyte cyclic AMP-phosphodiesterase (PDE) activity and increased in vitro IgE synthesis compared to normal (NL) subjects. Interleukin 4 (IL-4), interferon-gamma (IFN-γ), and PDE inhibitor have been shown to regulate in vitro IgE synthesis. This study investigated whether soluble T-cell factors such as IL-4 and IFN-γ could account for elevated PDE activity in patients with AD. Both rhIL-4 and IFN-γ significantly increased normal monocyte PDE activity to a maximum of 188% (n = 6, p < 0.05) and 315% above control (n = 3, p < 0.05), respectively. At concentrations below 0.1 units/ml IL-4 and IFN-y had synergistic effects on activation of monocyte PDE. AD and NL T-cell culture supernatants also significantly stimulated normal monocyte PDE activity, but the stimulatory activity was not significantly greater in the AD T-cell supernatants. The effect of both cytokines and T-cell supernatants on normal monocytes was inhibited by antibodies against IL-4 and IFN-γ, respectively. This study demonstrates that IL-4 and IFN-γ can increase PDE activity in normal monocytes. Though the levels of IL-4 and IFN-γ in T-cell supernatants are undetectable with an enzyme-linked immunosorbent assay (ELISA) assay, the concentration of these cytokines below the detectable level can significantly increase PDE activity of monocytes in a synergistic and dose-dependent manner. These results suggest that cytokine-mediated activation of monocytes can increase PDE activity. Furthermore, lymphokines may play an important role in modulating the cyclic nucleotide regulatory pathway.
AB - Patients with atopic dermatitis (AD) have elevated leukocyte cyclic AMP-phosphodiesterase (PDE) activity and increased in vitro IgE synthesis compared to normal (NL) subjects. Interleukin 4 (IL-4), interferon-gamma (IFN-γ), and PDE inhibitor have been shown to regulate in vitro IgE synthesis. This study investigated whether soluble T-cell factors such as IL-4 and IFN-γ could account for elevated PDE activity in patients with AD. Both rhIL-4 and IFN-γ significantly increased normal monocyte PDE activity to a maximum of 188% (n = 6, p < 0.05) and 315% above control (n = 3, p < 0.05), respectively. At concentrations below 0.1 units/ml IL-4 and IFN-y had synergistic effects on activation of monocyte PDE. AD and NL T-cell culture supernatants also significantly stimulated normal monocyte PDE activity, but the stimulatory activity was not significantly greater in the AD T-cell supernatants. The effect of both cytokines and T-cell supernatants on normal monocytes was inhibited by antibodies against IL-4 and IFN-γ, respectively. This study demonstrates that IL-4 and IFN-γ can increase PDE activity in normal monocytes. Though the levels of IL-4 and IFN-γ in T-cell supernatants are undetectable with an enzyme-linked immunosorbent assay (ELISA) assay, the concentration of these cytokines below the detectable level can significantly increase PDE activity of monocytes in a synergistic and dose-dependent manner. These results suggest that cytokine-mediated activation of monocytes can increase PDE activity. Furthermore, lymphokines may play an important role in modulating the cyclic nucleotide regulatory pathway.
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U2 - 10.1111/1523-1747.ep12611858
DO - 10.1111/1523-1747.ep12611858
M3 - Article
C2 - 1318907
AN - SCOPUS:0026650380
SN - 0022-202X
VL - 99
SP - 65
EP - 70
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -