TNFα

Abstract

Tumor necrosis factor α (TNFα) is essential for the maintenance of physiological immune homeostasis and is implicated in the pathogenesis of inflammatory and autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, graft-vs.-host disease, and septic shock. This chapter presents a study in which TNFα knockout mice appeared viable and fertile, and showed no apparent gross phenotypic abnormalities, indicating that TNFα is not required for normal mouse development. The TNFα null mice readily succumbed to Listeria monocytogenes infection and showed reduced contact hypersensitivity responses. Furthermore, TNFα knockout mice were resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remained sensitive to high doses of LPS alone. TNFα-deficient mice lacked primary B lymphocyte follicles and follicular dendritic cell networks in their spleen, peripheral and mesenteric lymph nodes, and Peyer's patches, demonstrating the essential role of TNFα in the follicular organization of secondary lymphoid organs. Results of this study confirm the important role of TNFα in anti-bacterial host defense and LPS-induced sepsis, consistent with its role as a pro-inflammatory cytokine.