Background: We have previously shown increased expression of the CD4(+) cel
l chemoattractant IL-16 at sites of airway allergic inflammation. Little is
known about the significance of IL-16 in allergic inflammation and its rol
e in allergen-driven T-cell cytokine responses. Because IL-16 interacts spe
cifically 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 pro
duction 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, an
d IFN-gamma were determined by means of ELISA at different time points betw
een 2 and 6 days. Effects of IL-16 on antigen-induced cellular proliferativ
e responses were determined.
Results: No IL-4 protein was detected after antigen stimulation of PBMCs fr
om 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 dep
leted of CD4(+) cells. The addition of rhIL-16 in antigen-stimulated PBMC c
ultures 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 i
dentified after antigen stimulation. The addition of rhIL-16 in antigen-sti
mulated PBMC cultures significantly increased IFN-gamma levels (median, 255
.6 pg/mL; P < .05). Effects of rhIL-16 appear to be specific for antigen-st
imulated 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 produ
ction in nonatopic normal subjects.
Conclusion: These studies suggest that IL-16 can play a role in regulating
the production of cytokines seen in allergic states in response to antigen.