Studies using leukemia inhibitory factor (LIF) knockout mice and a LIF adenoviral vector demonstrate a key anti-inflammatory role for this cytokine in cutaneous inflammation

Previous work has implicated the cytokine leukemia inhibitory factor (LIF) in cutaneous inflammation, although results have differed as to whether LIF is pro- or anti-inflammatory in this setting. We examined edema, inflammat ory cell infiltration, and cytokine responses following CFA injection in th e adult mouse footpad. Inflammatory cell infiltration and edema are signifi cantly enhanced when CFA is injected in LIF knockout mice as compared with injection of wild-type littermates. Moreover, local injection of an adenovi ral vector encoding LIF suppresses both measures of inflammation. In contra st, injection of an adenoviral vector encoding beta -galactosidase has no d iscernable effect on inflammation. In addition, comparison of the CFA respo nses in LIF knockout vs wild-type skin reveals that LIF is an important reg ulator of IL-1 beta, IL-6, IL-7, IL-2R alpha, and IFN-gamma in cutaneous in flammation, These and our previous data indicate that both endogenous and e xogenous LIF are anti-inflammatory in the CFA model and that LIF is a key r egulator of the cytokine cascade. The results also indicate that adenoviral gene delivery can be an effective therapeutic approach in this paradigm.