IL-16 inhibits IL-5 production by antigen-stimulated T cells in atopic subjects.
BACKGROUND
We have previously shown increased expression of the CD4+ cell chemoattractant IL-16 at sites of airway allergic inflammation. Little is known about the significance of IL-16 in allergic inflammation and its role in allergen-driven T-cell cytokine responses. Because IL-16 interacts specifically with CD4+ T cells, we hypothesized that IL-16 released at sites of inflammation may modulate the pattern of cytokines produced by CD4+ T cells.


OBJECTIVE
We investigated the effects of exogenous rhIL-16 on cytokine production of PBMCs from atopic and nonatopic subjects in response to antigen and PHA.


METHODS
Primary cultures of freshly isolated PBMCs from ragweed-sensitive atopic subjects and nonatopic subjects were stimulated with ragweed or PHA in the presence or absence of rhIL-16. Supernatant levels of IL-4, IL-5, and IFN-gamma were determined by means of ELISA at different time points between 2 and 6 days. Effects of IL-16 on antigen-induced cellular proliferative responses were determined.


RESULTS
No IL-4 protein was detected after antigen stimulation of PBMCs from atopic subjects, whereas significant levels of IL-5 were measured on day 6 (median, 534.9 pg/mL). IL-5 secretion was abolished in PBMC cultures depleted of CD4+ cells. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly reduced the amount of IL-5 released (median, 99.8 pg/mL; P <.001). Detectable levels of IFN-gamma (median, 53.3 pg/mL) were identified after antigen stimulation. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly increased IFN-gamma levels (median, 255.6 pg/mL; P <.05). Effects of rhIL-16 appear to be specific for antigen-stimulated PBMCs in atopic subjects because rhIL-16 did not alter IL-5 or IFN-gamma production in response to PHA nor did rhIL-16 alter cytokine production in nonatopic normal subjects.


CONCLUSIONS
These studies suggest that IL-16 can play a role in regulating the production of cytokines seen in allergic states in response to antigen.
Pinsonneault
S
S
Hospital Ste-Justine, University of Montreal, Montreal, Canada.
El Bassam
S
S
Mazer
B
B
Cruikshank
W W
WW
Laberge
S
S
D000485:Allergens / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018929:Cell Culture Techniques; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism*; D019410:Interleukin-16 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000485:Allergens; D019410:Interleukin-16; D015848:Interleukin-5; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate