Differential suppression of dendritic cell cytokine production by anti-inflammatory drugs.
BACKGROUND
Various anti-inflammatory drugs are available for the treatment of skin disorders. In these diseases, untoward immune responses to endogenous and/or environmental antigens are initiated by maturation and polarization of dendritic cells (DC).


OBJECTIVE
To explore the suppressive effects of anti-inflammatory drugs on DC maturation and, in particular, polarization.


METHODS
Exposure of DC to nickel in vitro results in DC maturation and secretion of both type 1 and type 2 cytokines, thereby providing a model to study the effects of anti-inflammatory drugs on DC responses. The inhibitory effects of anti-inflammatory drugs (ciclosporin, dexamethasone, diclofenac, dimethylfumarate, hydrocortisone, lactoferrin, 1-alpha,25-dihydroxyvitamin D3) on DC maturation (CD83, CD86, HLA-DR, CXCL8) and polarization (type 1: IL-12p70, TNF-alpha; type 2: IL-10, CCL17) were studied.


RESULTS
All anti-inflammatory drugs, except for lactoferrin, had inhibitory effects on DC maturation. Hydrocortisone and dexamethasone exclusively suppressed the release of type 1 cytokines. A less pronounced, but similar profile was observed for dimethylfumarate and 1-alpha,25-dihydroxyvitamin D3. Ciclosporin suppressed both type 1 and 2 cytokines. In contrast, diclofenac suppressed only type 2 DC cytokine secretion.


CONCLUSIONS
The present results give more insight into the pharmacological effects of immunosuppressive drugs on the immune system, and can thereby contribute to a more rational selection of anti-inflammatory drugs for the treatment of inflammatory skin disorders.
Toebak
M J
MJ
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
de Rooij
J
J
Moed
H
H
Stoof
T J
TJ
von Blomberg
B M E
BM
Bruynzeel
D P
DP
Scheper
R J
RJ
Gibbs
S
S
Rustemeyer
T
T
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects*; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000187:drug effects; D054414:Chemokine CCL17 / Q000096:biosynthesis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006684:HLA-DR Antigens / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D000097802:CD83 Antigen
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D051940:B7-2 Antigen; D054414:Chemokine CCL17; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen