Down-regulating effects of IL-4 and IL-10 on the IFN-gamma response in atopic dermatitis.
Atopic dermatitis (AD) is a chronic allergic disease associated with toxin (superantigen)-producing Staphylococcus aureus skin infections, impaired delayed hypersensitivity responses, and the expansion of IL-4-secreting Th2 cells, as well as diminished IFN-gamma synthesis. IL-12 is known to induce IFN-gamma synthesis and to augment Th1 responses. In this study, therefore, we examined the potential role of IL-12 in the immunopathogenesis of AD. We show that, after stimulation with staphylococcal toxic shock syndrome toxin-1 (TSST-1) or IL-12, PBMC from patients with AD are deficient in their ability to produce IFN-gamma. PBMC from AD patients, however, produced normal quantities of IL-12 and expressed normal levels of IL-12R. Induction of IFN-gamma by TSST-1 was decreased by neutralizing anti-IL-12 Ab in normal donors, but not in AD patients. The latter observation is consistent with a defective response to IL-12 in AD PBMC. Because AD is associated with increased production of IL-4 and IL-10, we examined the effect of IL-4 on IL-12- or TSST-1-induced IFN-gamma production in normal donors. IL-4 inhibited IL-12-induced IFN-gamma production. Furthermore, Ab neutralization of IL-4 caused increased production of IFN-gamma in AD PBMC. However, neutralization of IL-10 activity caused an even greater augmentation of IFN-gamma production. Our data suggest that despite normal levels of IL-12 production and IL-12R expression, PBMC from AD patients are unable to generate normal IL-12-induced IFN-gamma responses. This defective response may be due to the excess production of IL-4 and IL-10 in this common allergic condition.
Lester
M R
MR
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Hofer
M F
MF
Gately
M
M
Trumble
A
A
Leung
D Y
DY
D000293:Adolescent; D000328:Adult; D000368:Aged; D001427:Bacterial Toxins; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000032:analysis; D053707:Receptors, Interleukin-12; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D010835:Phytohemagglutinins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma