ZIDOVUDINE POTENTIATES LOCAL AND SYSTEMIC INFLAMMATORY RESPONSES IN THE RAT

The effect of chronic treatment with zidovudine (AZT) on the inflammat ory response was examined in the rat. AZT was administered orally for 36 days. On day 35, inflammation was induced by hindpaw injection of 1 % carrageenan lambda. Paw edema over a 24-hour period was used as a ma rker of the local inflammatory reaction. On day 36, quantification of immunoreactive T-kininogen and alpha(1)-inhibitor-3 in liver and serum was used to assess the systemic inflammatory response. Albumin was se lected as a protein whose concentration is modified only slightly or n ot at all during the acute-phase response. Animals treated with AZT tr ansiently exhibited significantly greater (18%) paw edema 3 hours afte r carrageenan injection. AZT treatment alone induced a 1.8-fold increa se in serum T-kininogen concentration, but it had no effect on albumin and alpha 1-inhibitor-3. In rats with inflamed paws, AZT administrati on led to a significant increase in liver (3.4-fold) and serum (1.8-fo ld) immunoreactive T-kininogen content. Dot blot analysis of total RNA isolated from liver correlated with the protein measurements. Our res ults indicate that chronic treatment with AZT potentiates the nonspeci fic local and the systemic inflammatory responses in the rat.