Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses.
In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.
Iwaz
J
J
Laboratory of Immunology, INSERM U.80, CNRS UA 1177, Hôpital E. Herriot, Lyon, France.
Kouassi
E
E
Lafont
S
S
Revillard
J P
JP
D000328:Adult; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D015536:Down-Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013806:Theophylline / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D002772:Cholera Toxin; D013806:Theophylline; D000242:Cyclic AMP