Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats

Abstract

The effect of human recombinant tumor necrosis factor-alpha (TNF) on experimental allergic encephalomyelitis (EAE) was studied in Lewis rats. TNF was injected intraperitoneally at a daily dose of 1 x 10(3) or 2 x 10(4) U for 8 consecutive days from one day after sensitization with guinea-pig spinal cord in complete Freund's adjuvant. All rats in the control group developed clinical signs of EAE but recovered within 8 days after the onset. Injections of 2 x 10(4) U/day of TNF resulted in a significant prolongation of clinical EAE: clinical signs were sustained for up to 15 days after onset. Histologically, rats receiving 2 x 10(4) U/day of TNF had more severe cellular infiltrations in the spinal cord than controls. The augmentation of EAE was not found in rats receiving 1 x 10(3) U/day of TNF or TNF that had been neutralized with anti-TNF monoclonal antibody.