Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial

Abstract

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.

Is systemic sclerosis an antigen‐driven T cell disease?

“…IFN␥ may also have a favorable effect on patients with SSc (90)(91)(92)(93). The importance of Th1/Th2 cytokines in fibrosis is supported by the finding that MRL/lpr mice lacking the IFN␥ receptor gene exhibit a syndrome that resembles human SSc (94).…”

Effect of IL-12 Encoding Plasmid Administration on Tight-Skin Mouse

“…Although the pathogenesis of SSc is still unknown, SSc can be considered a Th2 mediated disease, since its collagen synthesis has been shown to be activated by Th2 cytokines such as IL-4 (3, 4) and IL-6 (26). While previous studies demonstrated that IFN-␥ has been effective for SSc (27), its practical usage is limited because of its side effects (28). IL-12 has a strong effect on induction of IFN-␥ production in vivo.…”

Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?

“…287,288 Randomized trials of D-penicillamine, interferon-␣, or methotrexate either are no better than placebo or improve skin score with little beneficial effect on visceral organ function. [289][290][291] An exception is pulse intravenous cyclophosphamide, which appears to ameliorate scleroderma-related pulmonary alveolitis. 292 Scleroderma may be a vasculopathy, connective tissue disorder, and/or immune-mediated disease.…”