Therapeutic Use of Recombinant Interleukins

THERAPEUTIC USE OF RECOMBINANT INTERLEUKINS

In general, the approach to the development of ILs as a therapeutic modality is even more complex than for IFNs. Most ILs are embedded in a regulatory network and so far the pharmacological use of ILs has been somewhat disappointing. This was largely due to our lack of understanding of the role of these molecules and of the best way to use them; they are less well studied than IFNs. IL-2, for example, was initially developed by oncologists in the days when “go in fast, hit them hard and get out” was the prevalent strategy. Terms like maximal tolerated dose (which we called minimal poisonous dose) actually defined the dose at which a given drug was in most cases no longer tolerated. Thus IL-2 was given an undeserved bad reputation. Similar thinking nearly killed the devel-opment of IFNα for the treatment of chronic viral hepatitis and was ultimately the main reason for discontinuing the development of IL-2 in chronichepatitis B (Pardo et al., 1997; Artillo et al., 1998) and IL-12 in chronic hepatitis B and C (Zeuzem et al., 1999; Carren˜o et al., 2000; Pockros et al., 2003). In spite of this progress has been made and our understanding of the complexities of such substances and their antagonists is growing.