Impaired contact hypersensitivity to trinitrochlorobenzene in interleukin‐4‐deficient mice

We have examined the role of endogenously produced interleukin‐4 (IL‐4) in the contact hypersensitivity (CH) reaction to the haptene trinitrochlorobenzene (TNCB). The CH reaction was abolished in IL‐4 genetically deficient mice (IL‐4 KO), when compared to wild‐type (wt) mice. The CH reaction was restored by treatment with IL‐4 and further analysis revealed that IL‐4 exerted its action both at the induction and effector stages of the CH reaction. Despite failure to develop a CH reaction, IL‐4 KO mice developed a T helper type 1 (Th1) response to TNCB, in terms of lymphokine production in vitro. Furthermore, the number of Vγ3+ cells accumulating in the lymph nodes of TNCB‐immune IL‐4 KO mice was normal. The recruitment of mononuclear cells and vascular leakage at the challenge site were consistently reduced in IL‐4 KO mice and were restored by injection of IL‐4. This suggests that IL‐4 acts as a proinflammatory mediator in CH, perhaps favouring the accumulation of mononuclear cells at the site of inflammation. Among Th2‐type cytokines, IL‐13, but not IL‐10, was shown to restore the CH reaction to TNCB in IL‐4 KO mice. However, IL‐4 KO mice developed a normal CH response to oxazolone, indicating that IL‐4 was required for the CH reaction to TNCB, but not for that to oxazolone.