Interferon-gamma production in atopic dermatitis: a role for prostaglandins?
Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.
Byron
K A
KA
Department of Biochemistry, Royal Melbourne Hospital, Parkville, Australia.
Liberatos
S
S
Varigos
G A
GA
Wootton
A M
AM
D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology
D010835:Phytohemagglutinins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin