Differential suppression of dendritic cell cytokine production by anti-inflammatory drugs.

Abstract

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