* Microbiology and Tumor Biology Center, Karolinska Institutet, and
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
Correspondence: Dr. Hans-Gustaf Ljunggren, Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden. E-mail: hans-gustaf.ljunggren{at}mtc.ki.se
The administration of cAMP-elevating agents affects a number of
autoimmune and inflammatory conditions. Because dendritic cells (DCs)
play a pivotal role in autoimmunity and inflammation, the isolated
effects of cAMP-elevating agents on the function of DCs was examined.
In a dose-dependent manner, 8-Bromo cAMP, prostaglandin
E2, and 3-isobutyl-1-methylxanthine inhibited tumor
necrosis factor 
release and suppressed antigen presentation by DCs.
The same effect was observed with rolipram, a specific inhibitor of
phosphodiesterase type 4, but not with inhibitors of other
phosphodiesterases. The decreased antigen presentation by DCs was
associated with an enhanced production of interleukin (IL)-10 and with
lower major histocompatibility complex type II (MHC II) expression.
Furthermore, the inhibition of antigen presentation and MHC II
expression was significantly reversed by treatment of DCs with
neutralizing antibody against IL-10, suggesting the involvement of an
IL-10-dependent mechanism. Taken together, these results might explain
why certain cAMP-elevating agents such as rolipram are effective in
blocking autoimmunity and inflammation.
Key Words: antigen presentation • cytokines • drug inhibitors • lipopolysaccharide
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