Biochemical Host Response to Interferon-β

Abstract

To assess influence of host response to interferon-β (IFN-β), on biochemical parameters, β_-microglobulin (β₂-M) and neopterin were evaluated in 15 and 12 patients respectively before and 24 h after 1-46 × 10⁶ IU intravenously (i.v.) IFN-β given every other day. In 4 additional patients, both molecules were determined before and after 24, 48, 72, and 96 h of weekly IFN-β injections. Serum β²-M levels significantly increased 24 h after IFN-β administration in the overall group of 15 patients treated with the alternate day schedule (p = 0.003) as well as in the group of patients treated with the weekly schedule (p = 0.00003). Maximum induction of β₂-M was observed 24 h after a single weekly IFN-β injection, but the levels of this protein 72 h after still remained significantly higher than baseline values (p = 0.001). This demonstrates the progressive accumulation of β₂-M in the circulation produced by the continuous IFN administration. Nevertheless, in patients treated with both IFN treatment schedules, a clear correlation between the increments of β₂-M and the IFN-β doses was observed (p = 0.00002 and p = 0.0016 for the alternate day and the weekly schedule respectively). Furthermore the under curve area (AUC) of 48 h β₂-M levels after IFN administration significantly rose (p < 0.05) with increasing IFN doses in 4/6 patients. In spite of the accumulation of β₂-M in the circulation, the overall serum values of this protein 24 h after each successive IFN-injection, in the 15 patients receiving the alternate-day treatment, were significantly higher than before the immediate preceding dose both in patients with initially normal and those with initially high base levels (p = 0.00055 and p = 0.011, respectively). As with β₂-M, neopterin levels significantly rose during IFN treatment (p < 0.05) in the group of patients as a whole. After single weekly IFN-β injections, maximum induction of neopterin was observed 24 h after administration, then the levels of this molecule slowly declined towards the baseline levels, but 96 h after, its levels were still significantly elevated (p < 0.00001). Neopterin induction was not related to IFN-β doses, but the levels of this molecule both before and after IFN administration were correlated with an increase in the number of IFN injections (p = 0.0006 and p = 0.0009, respectively). Although neopterin progressively accumulated during the overall period of IFN treatment, 24 h after each secessive IFN injection, further increases of this molecule were observed (p = 0.0176). Levels of interleukin-1β (IL-1β), like neopterin a molecule produced by activated macrophages, showed no alteration in response to IFN-β treatment. Changes in serum levels of both β₂-M and neopterin represent suitable biochemical markers for monitoring IFN-β therapy, and might be used in future trials with this type of IFN to better define the relationship between biological effects and therapeutic outcome.