Proinflammatory potential of cytomegalovirus infection - Specific inhibition of cytomegalovirus immediate-early expression in combination with antioxidants as a novel treatment strategy?

We observed the effects of antiviral therapy on CMV and/or oxidative-stress -induced stimulation of proinflammatory molecules including interleukin-8 ( IL-8), melanoma growth stimulatory activity-alpha (GRO-alpha) and intercell ular adhesion molecule 1 (ICAM-1) using human foreskin fibroblasts, Gancicl ovir, foscarnet or cidofovir completely suppressed virus replication, as de monstrated by CMV late (L) antigen production, These drugs did not influenc e CMV immediate-early (IE) antigen expression and had no effects on CMV-ind uced cellular changes in IL-8, GRO-alpha and ICAM-1 levels, Phosphorothioat e oligonucleotide (ISIS 2922) suppressed both CMV IE and L antigen by 99%, ISIS 2922 completely suppressed CMV-induced upregulation of both chemokines and ICAM-1. Induction of oxidative stress by H2O2 upregulated IL-8 express ion. Oxidative stress and CMV infection showed synergistic effects on IL-8 expression. ISIS 2922 only partially inhibited the upregulation of IL-8 in infected cells treated with H2O2, whereas cotreatment with ISIS 2922 and an tioxidants inhibited the upregulation almost completely, The results showed that inhibition of CMV IE expression alone or in combination with antioxid ants is promising for the treatment of CMV disease. Copyright (C) 2000 S. K arger AG, Basel.