Synergistic effects of interleukin 4 and interferon-gamma on monocyte phosphodiesterase activity.
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-gamma), 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-gamma could account for elevated PDE activity in patients with AD. Both rhIL-4 and IFN-gamma significantly increased normal monocyte PDE activity to a maximum of 188% (n = 6, p less than 0.05) and 315% above control (n = 3, p less than 0.05), respectively. At concentrations below 0.1 units/ml IL-4 and IFN-gamma 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-gamma, respectively. This study demonstrates that IL-4 and IFN-gamma can increase PDE activity in normal monocytes. Though the levels of IL-4 and IFN-gamma 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.
Li
S H
SH
Department of Dermatology, Oregon Health Sciences University, Portland 97201.
Chan
S C
SC
Toshitani
A
A
Leung
D Y
DY
Hanifin
J M
JM
D003876:Dermatitis, Atopic / Q000097:blood; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000201:enzymology*; D009500:Neutralization Tests; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology
D015847:Interleukin-4; D007371:Interferon-gamma; D010727:Phosphoric Diester Hydrolases