A NOVEL ENDOGENOUS MEDIATOR OF CUTANEOUS INFLAMMATION - LEUKEMIA INHIBITORY FACTOR

Keratinocytes produce a variety of cytokines, including leukemia inhib itory factor. We hypothesised that this cytokine may play a pro-inflam matory role in the skin and tested this hypothesis by injecting recomb inant leukemia inhibitory factor (1-100 ng) into the ear pinnae of C3H /HeJ mice. To other groups of animals, we injected boiled leukemia inh ibitory factor or phosphate-buffered saline (negative control) or 0.4 ng human interleukin-1 alpha as a positive control. Following injectio n of 100 ng leukemia inhibitory factor, ear thickness, measured by mic rometer, 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 i ncreased by 67% at 6 h, 100% at 12 h and 340% after 24 h (overall p le ss than or equal to 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 inhibi tory factor and a 12-fold increase with 100 ng leukemia inhibitory fac tor, which remained elevated (17-fold) at 24 h (overall p = 0.0001). I njection of interleukin-1 alpha led to a 3.4-fold increase in leukocyt es (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 less than or equal to 0.0 0001). These results demonstrate that leukemia inhibitory factor appea rs to be a mediator of cutaneous inflammation.