Interleukin-2 and regulatory T cells
In the December 1st issue of the New England Journal of Medicine are two very interesting reports. The first from Koreth et al (2011; 365:2055-66) has studied the use of low dose interleukin-2 (IL-2) in chronic graft versus host disease following allogeneic haematopoietic stem cell transplantation for haematologic cancer that was resistant to steroid therapy. Patients received subcutaneous IL-2 at three dose levels but all representing low doses of IL2. All patients had a major increase in the population of T regulatory (Treg) cells and of the 29 patients enrolled a number had a significant clinical response.
The second study from Saadoun et al (2011;365:2067-77) investigated the use of low dose IL-2 in 10 patients with hepatitis C virus (HCV) induced vasculitis that was resistant to conventional anti viral therapy, rituximab therapy or both. There was an increase in Treg cells in these patients and there was a reduction in cryoglobulinemia in 9 of the 10 patients and an improvement in vasculitis in 8 of the 10 patients in the study. There were no adverse effects.
These two studies are of course very much phase 1 studies but are good examples of what may become a feasible therapy in patients with conditions associated with an immune dysfunction and a deficiency of Treg cells. In the same issue Jeffrey Bluestone has written an excellent editorial covering these two papers and others that are relevant. The title of his editorial is the “Yin and Yang of Interleukin-2 mediated immunotherapy” This is very appropriate in that we are already familiar with the fact that IL-2 can lead to an expansion of effector cells in high doses but in low doses it stimulates the proliferation of Treg cells. He points out that overall, low dose IL2 appears to be safe and that serious complications or infections occurred in very few patients. Furthermore increasing Treg cells did not lead to a recurrence of hematologic cancer in the patients with graft versus host disease although the graft versus host disease was suppressed nor in the HCV vasculitis patients was there any evidence of a worse viral load following the expansion of the Treg population. However long term follow up is required to see if the delicate balance between Treg and T effector cells is maintained.
As interest in Treg cells and their potential use in immunotherapy grows, these two papers do represent a significant contribution to our knowledge in this area.
