Abstract
Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8+ T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology.
Highlights
One dilemma in clinical practice when treating autoimmune patients is how therapies efficiently control autoimmunity without the pitfall of immunosuppression [1]
Our findings show that Low-dose IL-2 therapy might benefit autoimmune disease patients with increased risk of infection due to compromised immunity, such as reduced CD8+ T cell function, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology
Using rheumatoid arthritis as an example, clinical studies showed that glucocorticoid is a strong risk factor for increased infection [14,15], with those receiving over 10 mg of glucocorticoid per day increasing their risk of hospitalization from 6.78% to 13.25% [16]
Summary
Opportunistic infections cause disease exaggeration in patients with autoimmune diseases, representing a leading cause of mortality. Council (NHMRC) project GNT1147709, and the Bellberry-Viertel Senior Medical Research fellowship (to D.Y.). Promising new therapy to treat a wide range of inflammatory and autoimmune disorders, but the effect of this therapy to infections has not been systemically evaluated. In this retrospective study, Low-dose IL-2 therapy was found to be associated with the reduced incidence of infection in systemic lupus erythematosus (SLE) patients. Our findings show that Low-dose IL-2 therapy might benefit autoimmune disease patients with increased risk of infection due to compromised immunity, such as reduced CD8+ T cell function, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology
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