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Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay
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Prolonged elevation of intracellular cyclic AMP activates interleukin-1 production in human peripheral blood

E Serkkola1, M Hurme, T Palkama

  • 1Department of Bacteriology and Immunology, University of Helsinki, Finland.

Scandinavian Journal of Immunology
|February 1, 1992
PubMed

Insights

Elevated cyclic AMP (adenosine monophosphate) levels can activate interleukin-1 (IL-1) production in monocytes, but only when prolonged. Transient increases are insufficient, requiring inhibition of cyclic AMP degradation for activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Interleukin-1 (IL-1) is a key cytokine involved in inflammatory responses.
  • The role of intracellular cyclic AMP (adenosine monophosphate) in regulating IL-1 production is not fully understood.
  • Previous studies suggested transient increases in cyclic AMP do not induce IL-1 production.

Purpose of the Study:

  • To investigate the capability of elevated intracellular cyclic AMP concentration to activate IL-1 gene expression and protein production in human peripheral blood monocytes.
  • To determine the conditions under which cyclic AMP can effectively stimulate IL-1 production.

Main Methods:

  • Human peripheral blood monocytes were treated with prostaglandin E2 or forskolin to elevate cyclic AMP.
  • Isobutyl-methyl-xanthine (IBMX) was used to inhibit cyclic AMP degradation.
  • Dibutyryl cyclic AMP, a cell-permeant analogue, was also employed.
  • Bacterial lipopolysaccharide (LPS) was used as a positive control for IL-1 induction.
  • Cycloheximide was used to inhibit protein synthesis to study superinduction.

Main Results:

  • Transient elevation of cyclic AMP alone did not activate IL-1 production.
  • Inhibition of cyclic AMP degradation with IBMX, in combination with prostaglandin E2, strongly activated IL-1 production.
  • This effect was mimicked by high concentrations of dibutyryl cyclic AMP.
  • Cyclic AMP-induced IL-1 production exhibited slower kinetics compared to LPS-induced production.
  • IL-1 beta gene expression was superinducible by cycloheximide in the presence of cyclic AMP elevation.

Conclusions:

  • Prolonged elevation of intracellular cyclic AMP is a sufficient signal to activate IL-1 production in human monocytes.
  • The mechanism of cyclic AMP-induced IL-1 production differs from LPS-induced pathways, particularly in kinetics and regulation.
  • These findings provide new insights into the complex regulation of IL-1 by second messenger signaling pathways.

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