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

Abstract

SUMMARYReduced secretioti of IFN-7 in atopic itidividuals has been implicated iti the pathogenesis of disease, though the mechanisms leading to this reduced secretion have nol been elucidated. As production of IFN-'y has been shown to be predominantly regulated by its rate of transcription, expression of IFN-7 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-7 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-7 mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate ihat circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of Ihe inflammatory process in dVopic dermatitis. Although expression of IFN-7 mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(.'i) underlying reduced IFN-7 secretion in these individuals lie post-transcriptionally.

Effect of probiotics on vaccine antibody responses in infancy – a randomized placebo‐controlled double‐blind trial

“…Furthermore, interferon‐ γ is required for the induction of antibodies against polysaccharide epitopes (8, 18). Peripheral blood lymphocytes of atopic children produce less interferon‐ γ (30) but their defective interferon‐ γ production has been reversed by L. rhamnosus GG (1). Improved Hib antibody production of high‐risk infants in our probiotic group may thus reflect accelerated immune system maturation.…”

Spontaneous expression of IL-4 mRNA in lymphocytes from children with atopic dermatitis

“…Our present fmding of increased constitutive and stimulated IL-4 mRNA expression in PBMC from patients witb AD supports an increased Th2 aetivity in AD. However, we bave also examined iEN-'y mRNA expression in these patients, and found increased spontaneous iFN-7 expression witb detectable mRNA expression in six of tbe eigbt atopic patients [6]. A recent study of active atopic dermatitis skin lesions similarly reported more frequent expression of iFN-7 mRNA (13 of 15 patients) compared with iL-4 mRNA (four of 15 patients), as well as greater expression of iFN-7 mRNA than lL-4 mRNA in patients expressing bolh cytokines [44].…”

“…The fmding that anti-lL-4 antibody inhibits this spontaneous IgE production in peripheral blood mononuclear cell (PBMC) cultures from atopic individuals suggests that spontaneous TL-4 production in these cultures may contribute to the IgE synthesis [2,4], Spontaneous generation of other cytokines has been reported in atopic individuals. We have recently found increased interferon-gamma (lFN-7)-producing cells [5] and constitutive transcription of IFN-7 mRNA [6] in unstimulated PBMC cultures from children with atopic dermatitis (AD), and spontaneous secretion of lL-6 by T cells from adults with AD was documented by Toshitani et al [1]. These fmdings suggested that T cells had been activated in vivo.…”

The role of cytokines in atopic dermatitis: a breakthrough in immunopathogenesis and treatment

“…Interestingly, the IFN-Υ level fails to recover upon IL-2 stimulation, suggesting a potential intrinsic dysfunction (226). Although IFN-Υ mRNA transcripts are elevated, its release is reduced (227). Other studies found that IFN-Υ is spontaneously produced intracellularly, and that IFN-Υ-producing cells are rather increased in AD.…”