A novel endogenous mediator of cutaneous inflammation: leukemia inhibitory factor.
Keratinocytes produce a variety of cytokines, including leukemia inhibitory factor. We hypothesised that this cytokine may play a pro-inflammatory role in the skin and tested this hypothesis by injecting recombinant leukemia inhibitory factor (1-100 ng) into the ear pinnae of C3H/HeJ mice. To other groups of animals, we injected boiled leukemia inhibitory factor or phosphate-buffered saline (negative control) or 0.4 ng human interleukin-1 alpha as a positive control. Following injection of 100 ng leukemia inhibitory factor, ear thickness, measured by micrometer, increased 66% over controls at 12 h and 100% at 24 h (overall p = 0.041 by analysis of variance). Injection of 0.4 ng interleukin-1 alpha caused greater ear swelling. Compared with controls, swelling increased by 67% at 6 h, 100% at 12 h and 340% after 24 h (overall p < or = 0.00001). Leukemia inhibitory factor (100 ng only) stimulated a 3.5-fold increase in leukocytes after 6 h. After 12 h, a 14-fold increase was seen in ears injected with 10 ng leukemia inhibitory factor and a 12-fold increase with 100 ng leukemia inhibitory factor, which remained elevated (17-fold) at 24 h (overall p = 0.0001). Injection of interleukin-1 alpha led to a 3.4-fold increase in leukocytes (mean per 20 high-power fields) after 6 h, a 14-fold increase at 12 h and a 25-fold increase at 24 h (overall p < or = 0.00001). These results demonstrate that leukemia inhibitory factor appears to be a mediator of cutaneous inflammation.
McKenzie
R C
RC
Department of Dermatology, University of Edinburgh, Scotland.
Paglia
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D
Kondo
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Sauder
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DN
D000704:Analysis of Variance; D000818:Animals; D004431:Ear, External; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D007962:Leukocytes / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines