Dermatophagoides-induced interleukin-10 production by peripheral blood lymphocytes from patients with asthma in remission.
Interleukin (IL)-10 is a cytokine that regulates inflammatory responses. We studied the role of IL-10 in the development of tolerance to Dermatophagoides farinae in asthma patients in remission, since asthma improves in most children during adolescence. The spontaneous production of IL-10 by cultured peripheral blood mononuclear cells (PBMC) was higher in patients with active asthma than in normal subjects. IL-10 production decreased when 1 microg/ml D. farinae was added to cultures, but increased again in a dose-dependent manner when higher concentrations of D. farinae were added. In patients with remission of asthma, IL-10 production was lower than in patients with active asthma. However, production of IL-10 showed a reciprocal increase in the presence of 1 microg/ml D. farinae, and decreased again at 10 and 50 microg/ml D. farinae. Such alterations were not observed in normal subjects. Cell lines established from patients asthma in remission showed higher IL-10 production when compared with that by cell lines from normal subjects or patients with active asthma when the cells were stimulated by D. farinae at 1 or 10 microg/ml. Neutralization of IL-10 led to revival of the D. farinae-specific proliferative response of PBMC from patients in remission, which was otherwise decreased. The increase of IL-10 production stimulated by D. farinae was inhibited by addition of an anti-IL-10 antibody. In contrast, antigen-induced interferon (IFN)-gamma production, which was increased by D. farinae stimulation when patients were in remission, did not increase after treatment with anti-IL-10, although spontaneous IFN-gamma production increased to the level seen after D. farinae stimulation. The reduced IL-4 production by cells from patients in remission after stimulation with D. farinae antigen, which was significantly higher in active patients, was not reversed by neutralization of IL-10. The D. farinae-induced IL-10/IL-4 production ratio, but not the IL-10/IL-5 production ratio, may be a significant indicator for evaluation of whether a patient has been in remission. In conclusion, D. farinae-specific anergy of T cells is likely to be induced by increased levels of IL-10 and IFN-gamma that are initially produced by specific T cells after exposure to relevant mite allergen in patients in remission.
Department of Pediatrics, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. nomatake@med.kitasato-u.ac.jp
Takeshi
T
Noma
Yoko
Y
Sugawara
Norifumi
N
Ogawa
Tosiaki
T
Saeki
Koichi
K
Yamaguchi
Yutaka
Y
Kawano
D000293:Adolescent; D000328:Adult; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D039981:Pyroglyphidae / Q000276:immunology*; D012075:Remission, Spontaneous
D039741:Antigens, Dermatophagoides; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma