Type I interferon therapy and its role in autoimmunity

Abstract

Interferons (IFNs) display a pleiotropic effect on different cell types of both the innate and the adaptive immunities being able to affect the immune responses. The ability of IFNs, and in particular of type I IFN, to activate dendritic cells and to modulate the expression of major histocompatibility classes I and II molecules supports their potential role also in the development and maintenance of tolerance. When tolerance breakdown has occurred, immunocomplexes generated by the reaction of nuclear antigens and specific autoantibodies can further induce type I IFN production. Accordingly, high acid-labile type I IFN plasma levels, overexpression of IFNalpha-induced transcripts and the association with genes closely related to type I IFN response represent the rationale for the so-called IFN signature in systemic lupus erythematosus, a prototypical autoimmune disease. The role of IFNs in autoimmunity is further supported by their direct and deleterious impact on target tissues. The therapeutic use of IFNs is based on their antiviral and antiproliferative effect. Type I IFN administration, in particular, is associated with the appearance of autoimmunity, although less frequently than expected. Such an event takes place mostly in patients with previous autoimmune manifestations and can be characterized by the appearance of autoantibodies only or of a clinically overt disease. IFN therapy cessation is usually, but not always, required for controlling the autoimmune disorders.

Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens

“…Indeed, overexpression of IFNencoding genes may protect against experimental infection and inflammatory disease, and administration of recombinant IFN is commonly used for infectious, autoimmune, and cancerous conditions in humans (136). Unfortunately, this approach is limited by toxicity, because disproportionate levels of IFN might harm the normal host (137). It might therefore be more prudent to aim to increase the efficiency of the endogenous IFN signaling pathway and thereby potentiate the benefits of downstream ISG expression (44).…”

Dcp2 Decapping Protein Modulates mRNA Stability of the Critical Interferon Regulatory Factor (IRF) IRF-7

“…We propose that the functional consequence of increased Dcp2 would be a reduction of IRF-7 mRNA to temper the antiviral immune response. One significant outcome of such a mechanism could be to prevent excess production of IFNs to curtail the manifestation of autoimmune pathologies such as those that have been observed with therapeutic type I IFN administration (2). Whether negative regulation of the antiviral immune response by Dcp2 could be a protective mechanism against deleterious overexpression of IFNs remains to be determined.…”

Severe deterioration of newly diagnosed Takayasu arteritis in a patient re-treated with interferon beta-1α for concomitant longstanding multiple sclerosis

“…However, treatment with IFN beta-1a can cause or exacerbate existent autoimmune diseases [6][7][8]. To date, no guidelines exist with regard to the use of IFNs in patients with autoimmune diseases, but judicious use seems prudent [9]. In this study, we present a patient with new onset of Takayasu arteritis and concomitant MS who experienced a severe relapse of the arteritis after treatment with IFN beta1a for MS.…”