[Interferon-alpha and auto-immunity]

Abstract

Purpose: To assess the role of endogenous interferon alpha (IFN) in auto-immune experimental models and human diseases, and to evaluate its iatrogenic potential as a therapeutic agent.

Main points: IFN is a cytokine involved in cellular immunity, that promotes both differentiation of dendritic cells and the TH1 pathway. Auto-immune side-effects of recombinant IFN depend on IFN dosage and the pathology concerned. The spectrum extends from occurrence of auto-antibodies in an asymptomatic patient to overt disease such as systemic lupus. Antigenic targets of auto-antibodies are diverse: blood cells coagulation factors, immunoglobulin, hormones, intrinsic factor, intracellular components. Thyroiditis is the most frequently reported auto-immune disease occurring during IFN treatment, including hypothyroidism, hyperthyroidism or a bi-phasic pattern. Currently, true incidence of thyroiditis remains debated. It appears very low (under 1%) in hepatologic series using low-dose IFN. The fact that auto-immunity may be related to the treated disease--before use of IFN--must also be addressed: e.g. antinuclear factors and anti-DNA antibodies in chronic myeloid leukemia or anti-actin and anti-LKM antibodies in chronic C hepatitis.

Future prospects: Recombinant alpha interferon appears more as a trigger than a de novo inducer of auto-immune disorders. Its use as an immunomodulator agent should be treated with caution.