Inhibition of cytokine gene expression in mouse skin by subcutaneous injection of cyclosporine.
Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of action is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonstrated in vitro that CsA inhibits cell proliferation and suppresses cytokine gene expression in keratinocytes. In this study, we report the in vivo effects of CsA on skin cytokine gene expression as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleukin (IL)-1 alpha and tumor necrosis factor alpha gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited expression of all three genes by 80-90% relative to control levels. These data show that CsA can inhibit constitutive cytokine gene expression in mouse skin.
Kono
T
T
Division of Dermatology, University of Toronto, Sunnybrook Health Science Centre, Ont., Canada.
Kondo
S
S
Venner
T J
TJ
Sauder
D N
DN
McKenzie
R C
RC
D000818:Animals; D001483:Base Sequence; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D003864:Depression, Chemical; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine