Reduced interferon-gamma (IFN-gamma) secretion with increased IFN-gamma mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect

Abstract

Reduced secretion of IFN-gamma in atopic individuals has been implicated in the pathogenesis of disease, though the mechanisms leading to this reduced secretion have not been elucidated. As production of IFN-gamma has been shown to be predominantly regulated by its rate of transcription, expression of IFN-gamma mRNA was examined in atopic children and in age-matched, non-atopic controls by polymerase chain reaction (PCR)-assisted mRNA amplification. Children with atopic dermatitis were found to have constitutive expression of IFN-gamma mRNA in freshly isolated peripheral blood mononuclear cells (PBMC) and in unstimulated PBMC cultures which increased further following stimulation with phorbol myristate acetate (PMA)/Ca in vitro. In contrast, expression of IFN-gamma mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate that circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of the inflammatory process in atopic dermatitis. Although expression of IFN-gamma mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(s) underlying reduced IFN-gamma secretion in these individuals lie post-transcriptionally.