TNF-α is a potent mediator of immune and inflammatory responses. It is produced by many activated cell types including monocytes, astrocytes, granulocytes, T and B lymphocytes, NK cells, keratinocytes, fibroblasts, and certain tumor cells. Activated cells initially express TNF-α as a transmembrane protein that associates to form homotrimeric complexes. After proteolytic cleavage, the extracellular region of membrane TNF-α sheds as a soluble homotrimer. Membrane and soluble TNF-α homotrimers are biologically active whereas monomeric TNF-α is not. The mature mouse TNF-α monomer contains 156 residues, has a predicted size of ~17 kDa, and contains one potential N-glycosylation site. TNF-α exerts its biological activities by binding and signaling through membrane type I and II TNF-α Receptors (TNFR I and TNFR II). Interestingly, TNF-α binds to soluble forms of TNFRI and TNFRII which are naturally shed by activated cells and can modulate biological activities of TNF-α. TNF-α exerts many regulatory influences on the activation, growth, and differentiation of leukocytes and other cells. For example, TNF-α can co-stimulate differentiation of activated T and B lymphocytes, upregulate the expressed levels of MHC class I and class II molecules by various cell types, and induce the expression of adhesion molecules by endothelial cells. TNF-α is selectively cytotoxic for some transformed cell lines and can exert cytotoxic effects against certain solid tumors. In vivo, TNF-α serves as a primary mediator in protective immune responses against microbial and viral pathogens. Interestingly, TNF-α has also been implicated as a central mediator in a number of pathologic responses including septic shock, cachexia, and autoimmune diseases