Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia and Th2-type cytokine production in mice.
BACKGROUND
IL-16 has been described as a natural soluble CD4-ligand with immunosuppressive effects in vitro. However, little is known about the effect of IL-16 on immune responses in vivo.


OBJECTIVE
In the present study, we examined the effect of IL-16 administration in a murine model of allergic asthma. Next, we determined whether these effects were mediated by modulation of CD4+ T lymphocytes.


RESULTS
Intraperitoneal administration of IL-16 completely inhibits antigen-induced airway hyper-responsiveness and largely decreases the number of eosinophils in bronchoalveolar lavage fluid (> 90%) and airway tissue of ovalbumin-sensitized and challenged mice. Firstly, it appears that thoracic lymph node cells isolated from in vivo IL-16-treated ovalbumin-challenged animals produce less IL-4 (77%) and IL-5 (85%) upon antigenic re-stimulation, when compared to vehicle-treated mice. Secondly, pre-incubation of lymphocytes with IL-16 in vitro reduces antigen-induced proliferation (55%) and Th2-type cytokine production (IL-4; 56%, IL-5; 77%). Thirdly, the presence of IL-16 during priming cultures of TCR transgenic T cells (DO11.10), reduces IL-4 (33%) and IL-5 (35%), but not IL-10 and IFNgamma levels upon re-stimulation.


CONCLUSIONS
It can be concluded that IL-16 has potent immunosuppressive effects on a Th2dominated allergic airway response.
De Bie
J J
JJ
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Jonker
E H
EH
Henricks
P A J
PA
Hoevenaars
J
J
Little
F F
FF
Cruikshank
W W
WW
Nijkamp
F P
FP
Van Oosterhout
A J M
AJ
D000818:Animals; D000941:Antigens; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004802:Eosinophilia / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D019410:Interleukin-16 / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D016207:Cytokines; D019410:Interleukin-16; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin