Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.