Defective immune response and severe skin damage following UVB irradiation in interleukin‐6‐deficient mice

Abstract

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.

Role of IL-6 in Directing the Initial Immune Response to Schistosome Eggs

“…The finding that IL-6 induces IL-10 production as well as its role in inhibiting IFN-␥ may account for some of its antiinflammatory properties. Nishimura et al (31) have shown that IL-6 promotes IL-10 production using a model of UV-induced skin damage, and our results expand upon that finding by showing that IL-6 can enhance IL-10 production by CD4 and CD8 T cells after injection with schistosome eggs. The enhancement of IL-10 is implicated in the down-regulation of IL-12 seen after the addition of exogenous IL-6 to LN cultures from egg-injected WT mice.…”

Anti-aging effects of high molecular weight proteoglycan from salmon nasal cartilage in hairless mice

“…UVB irradiation induces inflammatory cytokines, such as interleukin-1, interleukin-6, and TNF-α (27)(28)(29)(30)(31)(32). Inflammation induced by UVB irradiation produces erythema (14) and subsequently leads to cutaneous hypertrophy (31).…”

Anti-aging effects of extracts prepared from salmon nasal cartilage in hairless mice

“…Inflammation by UV-B irradiation causes cutaneous hypertrophy (18). In addition, UV-B irradiation induces inflammatory cytokines such as interleukin-6 and TNF-α (19)(20)(21). Aggrecan may act with the immune system and inhibit inflammatory cytokines as an active anti-aging component.…”