Interferon response heterogeneity: activation of a pro-inflammatory response by interferon α and β. A possible basis for diverse responses to interferon β in MS

Abstract Interferon γ (IFN-γ) stimulates the (pro-inflammatory) type II interferon receptor and is known to exacerbate multiple sclerosis (MS). In contrast, IFN-α and IFN-β are ligands for the (anti-inflammatory) type I interferon receptor and are beneficial in some (but not all) patients with MS. Should IFN-β elicit a type-II-like pro-inflammatory response, the beneficial effects might be attenuated. These studies were undertaken to test this possibility with the use of quinolinic acid (QUIN) formation as a measure of type II receptor activation. In normal human macrophage cultures, IFN-γ was the most potent stimulus for QUIN formation. Generally, IFN-β and IFN-α were less potent. However, an unexpected inter-patient variability was observed. In some subjects, IFN-α was more potent than IFN-β. In other subjects, IFN-β was more potent than IFN-α. The present data demonstrate an inter-subject variability for QUIN production following exposure to the interferons. MS patients who demonstrate a pro-inflammatory response to IFN-β (e.g., increased QUIN) may be less likely to benefit from this therapy. J. Leukoc. Biol. 65: 439–443; 1999.