Hematopathology of interleukin 6-type cytokines

Interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) constitute a subfamily of cytokines on the basis of similar predicted structures and functional redundancy in their actions on a wide spectrum of cell types. Among the diverse targets of these pleiotropic factors are adipocytes, embryonic stem cells, hepatocytes, and cells belonging to the hematopoietic, immune and nervous systems. An explanation for the shared biologic activities of IL-6 subfamily members is provided by the finding that these cytokines trigger overlapping signal transduction pathways in responsive cells through a common receptor subunit, termed gp130. With the exception of CNTF, which appears to function primarily within the nervous system, IL-6-type cytokines differ from classical hormones in that they are synthesized by many tissues, frequently in association with disease states or in response to infection or injury. This article discusses the hematologic effects of dysregulated expression of IL-6 and related cytokines, highlighting results obtained in our laboratory with murine models of cytokine excess created by retroviral gene delivery to the hematopoietic system.