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

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