Dec 2, 2002
By Megan Rauscher
In patients with severe refractory psoriasis, treatment with recombinant human interleukin-4 (rhuIL-4) provides significant clinical benefit, and may represent a new therapeutic approach to other Th1-associated autoimmune diseases.
That's according to a report in the January issue of Nature Medicine posted online December 2nd. "This is the first clinical trial where IL-4 was given for the treatment of an inflammatory autoimmune disease in humans," team leader Dr. Martin Rcken of Eberhard Karls University Tuebingen, Germany, noted in comments to Reuters Health.
"This study was developed on the basis of preclinical studies, where we and others found that IL-4 deviates autoreactive T cells from an inflammatory phenotype (Th1) toward T cells with anti-inflammatory activities (Th2)," he added.
In this prospective dose-escalation trial, the research team had 20 patients with moderate to severe psoriasis self-inject rhuIL-4 in doses of 0.05, 0.1, 0.2, 0.3, or 0.5 g/kg subcutaneously three time daily, five days per week for six weeks.
Dr. Rcken and colleagues found that rhuIL-4 was well tolerated and, within six weeks, all patients showed decreased clinical scores and 15 saw a greater than 68% improvement in their condition. The overall efficacy of rhuIL-4 was "comparable to that achieved with photochemotherapy, which together with methotrexate, is the most effective therapy for psoriasis," the authors note.
After IL-4 treatment, 18 patients remained stable or continued to improve with treatments that had been ineffective prior to IL-4 treatment.
In psoriatic lesions, 0.2 to 0.5 g/kg rhuIL-4 reduced concentrations of two proinflammatory cytokines, IL-8 and IL-19, as well as the number Th1 cells carrying chemokine receptor CCR5, and the interferon-gamma/IL-4 ratio. In the circulation, rhuIL-4 increased the number of IL-4-producing CD4+ T cells two- to three-fold, but did not lead to overall immune suppression.
These findings, Dr. Rcken said, indicate that "in patients with inflammatory autoimmune diseases such as psoriasis immune responses are not fixed but remain flexible to therapeutic approaches." Therefore, it may be possible to "re-educate specifically autoreactive Th1 cells and to teach them to develop a more social or anti-inflammatory behavior, without inducing general immune suppression."
"The main hope is that this approach establishes the bases for the development of a vaccine strategy against inflammatory autoimmune diseases, such as psoriasis, multiple sclerosis, rheumatoid arthritis," he added.
Nat Med 2002. http://www.nature.com/naturemedicine
© 2002 Reuters Ltd