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We have recently demonstrated that G‐CSF promotes the generation of human T regulatory (TREG) type 1 cells. In this study, we investigated whether the immunomodulatory effects of G‐CSF might be mediated by DC. CD14+ monocytes were cultured with serum collected after clinical administration of G‐CSF (post‐G), which contained high amounts of IL‐10 and IFN‐α. Similar to incompletely matured DC, monocytes nurtured with post‐G serum acquired a DC‐like morphology, expressed high levels of costimulatory molecules and HLA‐DR, and exhibited diminished IL‐12p70 release and poor allostimulatory capacity. Importantly, post‐G DC‐like cells were insensitive to maturation stimuli. As shown by neutralization studies, IFN‐α and, even more pronounced, IL‐10 contained in post‐G serum inhibited IL‐12p70 release by post‐G DC‐like cells. Furthermore, phenotypic and functional features of post‐G DC‐like cells were replicated by culturing post‐G monocytes with exogenous IL‐10 and IFN‐α. Post‐G DC‐like cells promoted Ag‐specific hyporesponsiveness in naive allogeneic CD4+ T cells and orchestrated a TREG response that was dependent on secreted TGFβ1 and IL‐10. Finally, neutralization of IL‐10 and IFN‐α contained in post‐G serum translated into abrogation of the regulatory features of post‐G DC‐like cells. This novel mechanism of immune regulation effected by G‐CSF might be therapeutically exploited for tolerance induction in autoimmune disorders.

Few and contrasting data are available in the literature concerning the levels of various cytokines in blister fluid (BF) and in the serum of patients affected with bullous pemphigoid (BP). Using commercially available ELISA kits, this study reports the levels of 11 cytokines detected both in BF and sera of 15 BP patients and compares them with those of 15 control subjects' sera. Generally, no significant differences were observed in BP and control sera. In contrast, interleukin (IL) 1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) showed increased BF levels as compared with BP sera. Two cytokines, IL-11 and IL-12 did not show significant differences between BP BF and sera, while an opposite behaviour was observed for transforming growth factor beta 1 (TGF-beta 1), whose serum levels were higher than the concentrations in BF. Using the number of lesions of the patients as a possible disease intensity marker, significant correlations were found with the BF levels of IL-1 beta, IL-8, TNF-alpha and, most closely, IL-5. These data may have pathogenetic relevance and suggest the possibility that these biological modulators may be used as a quantitative marker of disease intensity.