The Role of Tumour Necrosis Factor-alpha (TNF-alpha) in Fever and the Acute Phase Reaction in Rabbits

We investigated the role of tumour necrosis factor-alpha (TNF-alpha) in fever and the acute phase reaction using a specific type-IV phosphodiesterase inhibitor, rolipram, that inhibits the production of TNF-alpha. The body temperatures and serum iron concentrations of rabbits were measured following injections of lipopolysaccharide (LPS) or Staphylococcus aureus (S. aureus) with either rolipram, diclofenac sodium or the appropriate control solutions. Rolipram significantly (P<0.05) inhibited the first phase of both LPS and Staphylococcal fever, but had no effect on the second phase. The fall in serum iron concentration was not significantly affected by the injection of rolipram together with LPS or S. aureus. These results suggest that TNF-alpha is a pyrogen that plays a role during the first phase of fever, at least. However, TNF-alpha appears not to mediate the fall in serum iron concentration during the acute phase reaction.