Failure to inhibit endotoxin-induced uveitis with antibodies that neutralize tumor necrosis factor

Many of the effects of bacterial endotoxin are attributed to the cytokines that it induces. Tumor necrosis factor alpha (TNFα) may be responsible for many of the pathophysiologic effects of endotoxin because antibodies that neutralize TNFα reduce endotoxin-induced mortality in experimental animals and many of the activities of endotoxin can be mimicked by the infusion of TNFα. Accordingly, we tested the ability of an antibody that neutralizes TNFα in a well characterized rat model, endotoxin-induced uveitis. Rats receiving subcutaneous endotoxin had a prompt rise in serum TNFα that was eliminated by the monoclonal antibody. Small quantities of TNFα were detectable in aqueous humor after either subcutaneous or intravitreal injection of endotoxin. Endotoxin-induced uveitis as quantitated by cells and protein in aqueous humor was, however, not affected by the antibody. Similarly, intraocular inflammation was not reduced by the intravitreal injection of the neutralizing antibody. Although TNFα may mediate many of the systemic effects of endotoxin, its role in the intraocular inflammatory effects of endotoxin should be questioned.