Involvement of cyclic adenosine monophosphate in the interleukin 4 inhibitory effect on interleukin 2-induced lymphokine-activated killer generation.

J Y Blay; D Branellec; E Robinet; B Dugas; F Gay; S Chouaïb

doi:10.1172/JCI114653

Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.

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Published in Volume 85, Issue 6 on June 1, 1990
J Clin Invest. 1990;85(6):1909–1913. https://doi.org/10.1172/JCI114653.
© 1990 The American Society for Clinical Investigation

Published June 1, 1990 - Version history

In previous studies, IL-4 has been reported to interfere with IL-2-driven generation of lymphokine-activated killer (LAK) activity. In this investigation, we have demonstrated that IL-4 inhibited the IL-2-induced differentiation of large granular lymphocytes (LGL) into LAK effectors by a mechanism involving, at least in part, an increase in LGL intracellular cAMP levels. In contrast, with its capacity to induce cAMP accumulation in resting LGL, IL-4 had a very negligible effect on LAK activity induction, and cAMP levels increase in LGL that had been preincubated with IL-2. Furthermore, the inhibitory effect of IL-4 on LAK activity generation also correlated with a marked decrease in N-CBZ-L-lysine thiobenzylester esterase activity, with an inhibition of tumor necrosis factor (TNF) mRNA expression and TNF production by IL-2-stimulated LGL. These results strongly suggest that complex signaling processes could be ascribed to the dual activities of cytokines and their interplay in LAK promotion.

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