Failure to inhibit endotoxin-induced uveitis with soluble TNF receptors

Endotoxin-induced uveitis is a standard model for acute onset ocular inflammation. Tumor necrosis factor (TNF) is a logical candidate to contribute to this inflammatory process. We investigated the activity of soluble TNF receptors as a potential inhibitor of endotoxin-induced uveitis. The soluble receptors were expressed as a dimeric fusion protein composed of two human (p80) TNF receptors coupled with the Fc portion of human IgG. Using either rats that received systemic endotoxin or rabbits that received intravitreal (i.vit.) endotoxin, the soluble receptors failed to reduce the ocular inflammatory process. Levels of the receptor in serum and aqueous humor suggested that receptors were present at a readily measurable level within the eye and blood. These observations indicate that inhibitors of systemic effects of endotoxin are not necessarily active in models of ocular inflammation.