TNF-alpha is secreted by macrophages, monocytes, neutrophils, T-cells (principally CD4+), and NK-cells. Many transformed cell lines also secrete TNF-alpha. TNF-alpha forms multimeric complexes; stable trimers are most common in solution. A 26 kD membrane form of TNF-alpha has also been described. TNF-alpha binding to surface receptors elicits a wide array of biologic activities including: cytolysis and cytostasis of many tumor cell lines in vitro, hemorraghic necrosis of tumors in vivo, increased fibroblast proliferation, and enhanced chemotaxis and phagocytosis in neutrophils.