Pleiotropic activities of human interferons are mediated by multiple response pathways.

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Human interferons (IFNs) exhibit pleiotropic effects, including antiviral activity, natural killer (NK) cell activation, and growth inhibition.
• Oxyphenbutazone is a nonsteroidal anti-inflammatory agent with known inhibitory effects on certain biological pathways.

Purpose of the Study:

• To investigate the effect of oxyphenbutazone on the antiviral, NK cell activation, and antigrowth activities of human alpha and beta interferons.
• To determine if oxyphenbutazone's inhibition of interferon activity is linked to prostaglandin biosynthesis.

Main Methods:

• Assessed antiviral activity using cytopathic effect and vesicular stomatitis virus assays in human foreskin fibroblasts.
• Measured NK cell activation and interferon-induced antigrowth activity in human breast carcinoma (MDA-MB-231) and vulvar carcinoma (A431) cell lines.
• Compared oxyphenbutazone's effects with other fatty acid cyclooxygenase inhibitors.

Main Results:

• Oxyphenbutazone potently inhibited the antiviral activity of human interferons in a dose-dependent manner.
• Oxyphenbutazone did not inhibit NK cell activation or interferon-induced antigrowth effects at concentrations up to 100 microM.
• Other cyclooxygenase inhibitors did not affect the antiviral activity of human interferons, indicating oxyphenbutazone's action is distinct from prostaglandin synthesis.

Conclusions:

• Oxyphenbutazone inhibits the antiviral cascade of human interferons at a site separate from prostaglandin biosynthesis.
• The selective inhibition of antiviral activity suggests a specific pathway targeted by oxyphenbutazone, distinct from NK cell activation and antigrowth effects.