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.

Methods and 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 IFNγ levels upon re‐stimulation.

Conclusion It can be concluded that IL‐16 has potent immunosuppressive effects on a Th2‐dominated allergic airway response.