Defective immune response and severe skin damage following UVB irradiation in interleukin-6-deficient mice.
Interleukin-6 (IL-6), a multifunctional cytokine, is induced in the acute-phase reaction following ultraviolet (UV) irradiation of humans and mice. Using IL-6-deficient (IL-6-/-) mice, we investigated the role of IL-6 in immunosuppression and inflammatory responses caused by UVB (280-320 nm) radiation. The IL-6-/- mice had a defective contact hypersensitivity (CHS) in response to the sensitizers 2,4-dinitrofluorobenzene and oxazolone. The injection of recombinant IL-6 (rIL-6) into these mice resulted in a marked recovery of the CHS. Serum IL-6 was significantly elevated by UV irradiation of wild-type B6 J/129Sv (IL-6+/+) mice but was not detectable in IL-6-/- mice. Interestingly, there was no induction of serum interleukin-10 (IL-10) by UV irradiation of IL-6-/- mice, whereas UV exposure caused a significant increase in serum IL-10 levels in IL-6+/+ mice. Injection of rIL-6 into IL-6-/- mice increased IL-10 to levels similar to those of IL-6+/+ mice. Being different from IL-6+/+ mice, no epidermal proliferation was found at 48 hr in the IL-6-/- mice, but delayed cell proliferation was observed at 72 hr after UV exposure. Immunohistochemical analysis demonstrated that the epidermis was capable of synthesizing IL-6 at 72 hr after UV irradiation of IL-6+/+ mice. In addition, the IL-6-positive cells appeared to be Langerhans' cells, which were detected with dendritic cell-reactive S-100 antibody. The present study strongly suggests that IL-6 may play a crucial role in the alteration of cutaneous immune responses following UV exposure, and provides evidence that IL-6 is a potent inducer of IL-10. Furthermore, IL-6 production induced by UV radiation appears to be an important early signal for repair of UV-caused skin damage.
Nishimura
N
N
Environmental Health Sciences Division, National Institute for Environmental Studies (NIES), Tsukuba, Japan.
Tohyama
C
C
Satoh
M
M
Nishimura
H
H
Reeve
V E
VE
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology / Q000528:radiation effects*; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000172:deficiency*; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D016753:Interleukin-10