DETERMINATIONS OF SERUM TUMOR-NECROSIS-FACTOR-ALPHA IN CORNEAL ALLOGRAFTS

Corneal allograft rejection culminates in a series of interactions bet ween different classes of antigen presenting cells, cytokines and leuk ocytes. Tumor necrosis factor-alpha (TNF-alpha) was recently reported to be elevated in acute rejection of solid organ transplants, This cyt okine is released early in immune activation and may be detected in th e peripheral circulation. Serial determinations of TNF-alpha serum lev els were performed following experimental corneal allografts. Lewis ra ts received 3.5 mm orthotopic corneal grafts of MHC-incompatible Wista r-Furth donors. TNF-alpha concentrations were measured in serum sample s collected pre- and postoperatively and measured by micro ELISA. Clin ical observations revealed graft rejection in 65.5 % of corneal transp lants 14 +/- 4 days following grafting. The mean serum level of TNF-al pha in control animals without corneal graft (group I) was 41 +/- 12 p g/ml. Animals following keratoplasty without allograft rejection (grou p II) showed a mean TNF-alpha level of 54 +/- 16 pg/ml that did not di ffer from group I. The rejection group III displayed significantly hig her TNF-alpha levels (98 +/- 16 pg/ml, p<0.05). These significantly el evated levels were found even before the diagnosis of rejection was es tablished by clinical criteria, These data suggest systemic immunoreac tivity to corneal allografts, Elevated levels of cytokines may provide valuable information in recipients undergoing rejection and may also provide a rationale for systemic immunotherapy in some instances.