Monoclonal antibodies against human recombinant tumor necrosis factor: prevention of endotoxic shock.

Six murine monoclonal antibodies, AT-1, 2, 3, 4, 5, and 6 were produced against human recombinant tumor necrosis factor (gamma TNF). AT-1, -2, -3, -4, and -6 were IgG1, and AT-5 was IgG2a. AT-1, -2, and -3 neutralized the activity of gamma TNF (2 X 10(3) U/ml) over a range of dilutions between 5 and 500 micrograms/ml of IgG, while AT-4, -5 and -6 failed to neutralize the activity in these concentrations. All the antibodies showed immunoprecipitating activity for gamma TNF (2 X 10(3) U/ml) over a range of dilutions between 0.5 and 500 micrograms/ml. The AT-6 was weaker than the rest. AT-1, which neutralized gamma TNF activity efficiently, and AT-4, which did not neutralize the activity, were used to protect mice against endotoxic shock. AT-1 protected mice from the lethal effects of endotoxin, while AT-4 failed to do so. AT-1, -2, and -3 also neutralized the activity of human and mouse natural TNF. AT-1, -2, and -3 neutralized the activity of gamma TNF, but not that of lymphotoxin (LT) and interferon (IFN).