Environmental antigen-induced IL-13 responses are elevated among subjects with allergic rhinitis, are independent of IL-4, and are inhibited by endogenous IFN-gamma synthesis.
Human immediate hypersensitivity diseases represent the most common example of chronic excessive Th2-like activation in developed nations. While IL-13 shares many functional properties with IL-4, the intensity and regulation of environmental Ag-stimulated IL-13 synthesis by allergic vs nonallergic individuals remain ill defined. Here, we examine the intensity of polyclonally and Ag-stimulated IL-13 production by PBMC of 20 subjects with seasonal allergic rhinitis and 20 healthy controls. Polyclonally driven IL-13 responses did not differ significantly (Mann-Whitney U test, p = 0.68). In contrast, the median CD4-dependent IL-13 response among atopics was markedly stronger than nonatopics in Ag-stimulated primary culture (p = 0.0031) and exhibited a strong correlation with IL-5 (r = 0.76, p = 0.0009), but not IL-4 (r = 0.14, p > 0.05), responses. IL-13 production was unaffected by blocking endogenous IL-4 or IL-5 activity or by addition of rIL-4 or rIL-5. In contrast, it was inhibited by low levels of rIFN-gamma and strongly enhanced upon addition of neutralizing anti-IFN-gamma mAb. Collectively, the data are consistent with a negative regulatory role for endogenous IFN-gamma synthesis in controlling the intensity of systemic IL-13 responses evoked in both atopic and nonatopic populations following exposure to common Ags. They also suggest that the elevated levels of IL-4 and IL-5 characteristic of type 2-dominated responses in vivo are without detectable impact on the maintenance of recall Ag-stimulated IL-13 production.
Li
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Department of Immunology, University of Manitoba, Winnipeg, Canada.
Simons
F E
FE
HayGlass
K T
KT
D000293:Adolescent; D000328:Adult; D000388:Air; D000485:Allergens / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D004781:Environmental Exposure; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011058:Pollen / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D015848:Interleukin-5; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma