Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone.
Mice rendered deficient in IL-1 beta by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1beta-deficient mice showed normal synthesis and cellular release of IL-1alpha after treatment with 5 mM ATP demonstrating that IL-1beta is not necessary for expression and release of the IL-1alpha isoform. Mice deficient in IL-1beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-1beta-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1beta immediately before antigen application. These data demonstrate an essential role for IL-1beta in contact hypersensitivity and suggest that IL-1beta acts early during the sensitization phase of response. They suggest an important role for IL-1beta in initiation of the host of response at the epidermal barrier.
Shornick
L P
LP
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
De Togni
P
P
Mariathasan
S
S
Goellner
J
J
Strauss-Schoenberger
J
J
Karr
R W
RW
Ferguson
T A
TA
Chaplin
D D
DD
D000818:Animals; D001483:Base Sequence; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D004817:Epidermis / Q000276:immunology; D018390:Gene Targeting; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010853:Picryl Chloride / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000276:immunology / Q000401:mortality
D007375:Interleukin-1; D011994:Recombinant Proteins; D010853:Picryl Chloride