Elsevier

Cytokine

Volume 7, Issue 1, January 1995, Pages 64-69
Cytokine

Regular Article
Role of Cyclic Nucleotides and Nitric Oxide in Blood Mononuclear Cell IgE Production Stimulated by IL-4

https://doi.org/10.1006/cyto.1995.1008Get rights and content

Abstract

The involvement of cyclic nucleotides and of phosphodiesterase activities in IL-4-induced IgE production and release of the soluble form of the low affinity receptor for IgE (sCD23) by normal human peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were stimulated by a suboptimal dose of IL-4 (10 ng/ml) cAMP inducers, adrenaline (ADR) and cholera toxin (CTx), which were found to potentiate IL-4-induced IgE production and sCD23 release after 12 days of culture. In the presence of an optimal dose of IL-4 (30 ng/ml), both ADR and CTx inhibited the production of both IgE and sCD23. In the presence of a chemical cGMP inducer, Sin-1, the production of IgE induced by 10 ng/ml IL-4 appeared to be potentiated whereas in the same experimental situation the sCD23 production was decreased. Sin-1 was found to inhibit the production of both IgE and sCD23 as effectively as cAMP inducers when an optimal dose of IL-4 was used. Since Sin-1 is a nitric oxide (NO) generating compound, we evaluated the possible involvement of the L-arginine metabolic pathway using a competitive inhibitor of L-arginine, NC-monomethyl-L-arginine (LNMMA). In the presence of 1 mM LNMMA both IgE and sCD23 production induced by either a sub-optimal or an optimal dose were partially inhibited (from 50 to 80% inhibition depending on the donor). The generation of cAMP and cGMP in the cells is controlled by cyclic nucleotide phosphodiesterases (CN-PDE), so we evaluated the effect of a CN-PDE inhibitor, isobutyl-methyl xanthine (IBMX), on the IL-4-induced IgE and sCD23 production. In the presence of 10μM IBMX the production of IgE and of sCD23 was up-regulated in the presence of either a sub-optimal or an optimal dose of IL-4. Taken together these data indicate that cyclic nucleotide metabolism and CN-PDE activities are important intracellular regulators of IL-4-induced IgE and sCD23 production by normal human PBMC.

References (0)

Cited by (0)

View full text