Epidermal cytokines in murine lupus.
Murine lupus and the analogous human disease systemic lupus erythematosus (SLE) in humans are characterized by multisystem disease accompanied by the production of numerous serum autoantibodies. The classic model of murine lupus is the New Zealand black mouse (NZB). In this strain anti-DNA antibodies are the most specific marker for the presence of murine lupus, in that this autoantibody parallels both the development and activity of the disease. Exposure to ultraviolet (UV) radiation is known to exacerbate the disease in both the murine and the human disease. UV irradiation of the skin increases serum levels of certain cytokines including interleukin-1 (IL-1), IL-6, and granulocyte/macrophage-colony stimulating factor (GM-CSF), which can influence B- and T-cell function. Recent studies have focused on the role of cytokines in SLE. We hypothesize that the ultraviolet (UV)-induced exacerbation in NZB mice in part is mediated by UV-induced cytokines such as IL-1. Eight-week-old female NZB and DBA/2 mice were exposed to UV irradiation. Sera and supernatants from spleen cell cultures were assayed for anti-DNA antibodies. After UV exposure, NZB mice showed a marked increase in such antibodies. Skin from both strains of mice was probed for IL-1 alpha mRNA before and after UV irradiation. At 24 h, DBA/2 mice had a slight increase in mRNA coding for IL-1 alpha, whereas a much greater increase in skin IL-1 alpha was seen in the NZB skin. This increase in IL-1 mRNA was associated with similar increases in IL-1 bioactivity. These data suggest that the mechanism underlying the UV-induced exacerbation of lupus is mediated in part by the cutaneous production of IL-1.
Sauder
D N
DN
Department of Medicine, University of Toronto, Ontario, Canada.
Wong
D
D
Laskin
C
C
D000818:Animals; D000917:Antibody Formation / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000276:immunology; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D007075:Immunoglobulin M / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008177:Lupus Vulgaris / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D012333:RNA, Messenger / Q000378:metabolism; D014466:Ultraviolet Rays
D016207:Cytokines; D004277:DNA, Single-Stranded; D007075:Immunoglobulin M; D007375:Interleukin-1; D012333:RNA, Messenger