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 Vgamma3+ 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.
Dieli
F
F
Institute of General Pathology, University of Palermo, Italy.
Sireci
G
G
Scirè
E
E
Salerno
A
A
Bellavia
A
A
D000276:Adjuvants, Immunologic; D000818:Animals; D002199:Capillary Permeability; D003877:Dermatitis, Contact / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000172:deficiency* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone; D010853:Picryl Chloride; D018417:Th1 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018836:Inflammation Mediators; D018793:Interleukin-13; D016753:Interleukin-10; D010081:Oxazolone; D015847:Interleukin-4; D010853:Picryl Chloride