Clinical tolerance and profile of cytokine induction in healthy volunteersfollowing the simultaneous administration of IFN-alpha and the synthetic immunomodulator murabutide

As the therapeutic use of interferon-alpha (IFN-alpha) is limited by a dose -dependent toxicity and variable efficacy, ways of improving the therapeuti c index of the cytokine are being sought. Murabutide (N-acetyl muramyl-L-al anyl-D-glutamine-O-n-butyl-ester) (ISTAC Biotechnology, Lille, France) is a safe synthetic and clinically acceptable immunomodulator that enhances the biologic activities of IFN-alpha in different experimental models. We eval uated in healthy human volunteers tolerance of the coadministration of Mura butide with increasing doses of IFN-alpha. The simultaneous administration of the two drugs was well tolerated without any increased or prohibiting to xicity, and all recipients experienced side effects that were similar to th ose observed after the administration of IFN-alpha alone. We also profiled the serum levels of cytokines induced following coinjection of the two drug s. We mostly detected an induction of anti-inflammatory cytokines and of hu man immunodeficiency virus type 1 (HIV-1)-suppressive beta -chemokines, in the absence of release of key proinflammatory cytokines. Therefore, the sim ultaneous administration of Murabutide and IFN-alpha is well tolerated and does not lead to increased toxicity. In addition, the selectivity in the pr ofile of cytokines and chemokines induced following the coadministration of Murabutide and IFN-alpha points to the potential use of this combination i n the treatment of inflammatory diseases and chronic viral infections.