Interaction of tumor necrosis factor and lymphotoxin with model lipid membranes

TNF and LT are two pleiotropic lymphokines produced mainly by activated macrophages and lymphocytes. TNF has recently been shown to damage liposome membranes. Here, we have tested recombinant TNF and LT (rTNF and rLT) on high-resistance planar lipid bilayers and assessed changes in transmembrane current. Under the conditions tested (pH range 4.5-8), membrane permeability was not altered by these cytokines alone or in combination with gamma-interferon, in marked contrast to previously published results. Moreover, less than 5% of rTNF and rLT bound to liposomes even under low pH conditions. These results suggest TNF and LT must interact with other cellular factors (perhaps receptors) in order to mediate their activity.