Anticytokine Therapies in Systemic Lupus Erythematosus
Anticytokine Therapies in Systemic Lupus Erythematosus
The dysfunctional immune response that characterizes systemic lupus erythematosus (SLE) associates with an unbalanced production of soluble mediators that are crucial in promoting and sustaining chronic inflammation. The successful use of biologics in several autoimmune diseases has led to studies in SLE aimed at contrasting the proinflammatory responses that contribute to tissue and organ damage in the disease. Several approaches have been developed and tested as potential therapeutic agents in SLE in preclinical studies and in clinical trials. This article provides an overview on antibody-based approaches in SLE that, although preliminary, have the potential to expand the current therapeutic possibilities in the disease.
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple tissues and systems and is characterized by significant interindividual variability in clinical manifestations and organ involvement. Despite new and improved therapeutic options having positively impacted the prognosis of SLE, some SLE patients experience an aggressive disease course and/or unresponsiveness to therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE (increased risk of infection, infertility and liver toxicity, among others) call for an improvement in the current therapeutic management of SLE.
From a pathogenesis standpoint, unbalanced immune homeostasis and aberrant autoreactivity in SLE associate with inflammatory cells and the production of autoantibodies that play key roles in the development of tissue damage. Since cytokines promote and/or sustain the proinflammatory environment, anticytokine therapies have come under scrutiny as new modalities to dampen or reduce the deleterious inflammatory responses associated with hyperactivity of immune cells and autoantibody production. The envisioned benefits could significantly affect patients that cannot tolerate or are unresponsive to conventional therapies. They could also prove beneficial in reducing dosages of immunosuppressive drugs (and thus side effects) and improving clinical control (e.g., reduce risk of flare-ups) in patients that respond to therapy.
Abstract
The dysfunctional immune response that characterizes systemic lupus erythematosus (SLE) associates with an unbalanced production of soluble mediators that are crucial in promoting and sustaining chronic inflammation. The successful use of biologics in several autoimmune diseases has led to studies in SLE aimed at contrasting the proinflammatory responses that contribute to tissue and organ damage in the disease. Several approaches have been developed and tested as potential therapeutic agents in SLE in preclinical studies and in clinical trials. This article provides an overview on antibody-based approaches in SLE that, although preliminary, have the potential to expand the current therapeutic possibilities in the disease.
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple tissues and systems and is characterized by significant interindividual variability in clinical manifestations and organ involvement. Despite new and improved therapeutic options having positively impacted the prognosis of SLE, some SLE patients experience an aggressive disease course and/or unresponsiveness to therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE (increased risk of infection, infertility and liver toxicity, among others) call for an improvement in the current therapeutic management of SLE.
From a pathogenesis standpoint, unbalanced immune homeostasis and aberrant autoreactivity in SLE associate with inflammatory cells and the production of autoantibodies that play key roles in the development of tissue damage. Since cytokines promote and/or sustain the proinflammatory environment, anticytokine therapies have come under scrutiny as new modalities to dampen or reduce the deleterious inflammatory responses associated with hyperactivity of immune cells and autoantibody production. The envisioned benefits could significantly affect patients that cannot tolerate or are unresponsive to conventional therapies. They could also prove beneficial in reducing dosages of immunosuppressive drugs (and thus side effects) and improving clinical control (e.g., reduce risk of flare-ups) in patients that respond to therapy.