IL-6 Gene Knockout Mice

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by a variety of cells, including macrophages, T-cells, B-cells, fibroblasts, and endothelial cells, in response to a wide range of stimuli and is thought to play regulatory roles in the immune system, the hematopoietic system, and the nervous system (1). This factor has been given at least nine different names each describing a single biological activity. It was originally identified as a T-cell factor which induced the terminal maturation of B-cells into antibody-producing plasma cells (2),but has also been shown to stimulate the differentiation of cytotoxic T-cells (3), the differentiation and/or proliferation of cells belonging to different hematopoietic lineages (4), and to be the major regulator of acute phase protein synthesis during the inflammatory response (5). In vitro, factors such as IL-1, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) display overlapping activities with IL-6 that may be explained by a common receptor signal transducing component (gp 130). In order to clarify the unique functions of IL-6 in vivo, we have disrupted the murine IL-6 gene in the second exon by insertion of a neon r cassette and derived mice homozygous for this mutation (6). Although IL-6 may be expressed as early as the eight-cell stage of embryonic development (7), the F1 was generated in the expected Mendelian pattern. Interbreeding resulted in normal numbers of pups with no obvious defects, suggesting that IL-6 is not crucial for embryonic development. In this chapter, we present data describing the roles of IL-6 in B- and T-cell function, hematopoiesis, and acute phase inflammatory responses obtained in studies using these IL-6-/- mice.