IL-10 and the Cytokine Network in the Pathogenesis of Human Autoimmune Hemolytic Anemia

Abstract

In animal and human autoimmune hemolytic anemia (AIHA) immunologic tolerance loss against RBC self-antigens could be originated by several mechanisms: ignored self-antigens' epitopes, polyclonal lymphocyte activation, molecular mimicry between self- and foreign antigens, central or peripheral tolerance errors, or immunoregulatory disturbances including the alteration of a cytokine network. To identify the immunologic factors contributing to autoimmune onset and maintenance, several murine strains (such as NZB and NZB/NZW) that spontaneously develop a complex autoimmune syndrome, including AIHA, have been extensively studied. In human AIHA, the respective roles of IL-2, IL-4, IFN-gamma, IL-10, and IL-12 were investigated by examining the spontaneous and mitogen-induced (OKT3 or LPS) production of these cytokines. ELISA methods were used in PBMCs to evaluate whether the manipulation of IL-10/IL-12 balance can have an effect on the incidence of autoimmune diseases and whether this might be useful for the control of AIHA. Results affirmed that AIHA is a disease that exhibits an increased basal synthesis of IL-4 and decreased levels of IFN-gamma by AIHA PBMCs compared with controls and that there is a basal increase of Th2 cytokines. Th1-type cytokine decrease in the basal state occurred in parallel with an increase of constitutive IL-10 production and an IL-12 decrease. In conclusion, decreased production of Th1-type cytokines and the production of autoantibodies in AIHA may be secondary to the imbalance between IL-10 and IL-12, and the neutralization of IL-10 may be efficacious in diminishing the clinical pathology associated with Th2 subset prevalence. In the same way, the treatment with IL-12 could offer a second and independent level of blockade against the consequences of the overstimulation of B cells associated with AIHA.

An association of interleukin-10 gene polymorphisms with Graves’ disease in two Chinese populations

“…IL-10, one of the major anti-inflammatory cytokines, is secreted by activated T cells, monocytes, B cells, and thymocytes. IL-10 has been found associated with several autoimmune diseases, such as encephalomyelitis and hemolytic anemia, which suggest that IL-10 might be a regulatory role involved in inflammation and reversing immune-pathology [15,16]. Interestingly, it was reported that the serum concentration of cytokine IL-10 was much higher in GD patients compared with controls [17].…”

Preconditioning with Hemin Decreases Plasmodium chabaudi adami Parasitemia and Inhibits Erythropoiesis in BALB/c Mice

“…The levels of the T h 2 type cytokines IL-4, IL-10 and IL-13 are relatively enhanced whereas IFN-γ responses are compromised in thalassemia, sickle cell disease (SCD) and autoimmune hemolytic anemia [1], [2], [3]. Malaria is a hemolytic disease also characterized by high levels of free heme in circulation, oxidative stress and inflammation [16], [32], and Plasmodium -infected hosts are particularly susceptible to bacterial and viral infections, as are people with genetic hemolytic disorders [33], [34], [35], [36].…”

“…Malaria and other hemolytic disorders are characterized by enhanced susceptibility to bacterial and viral infections, and increased levels of IL-4, IL-6 and IL-10 [1], [2], [3]. These reports suggest a T helper (T h ) 2 bias in chronic and acute hemolytic conditions that may contribute to altered cellular immunity.…”

Inhibitory effects of thyroxine on cytokine production by T cells in mice

“…IFN-γ and IL-2 belonging to T-cell type I cytokine are responsible for cellular immune responses, while IL-4 and IL-10 being ascribed to T-cell type II cytokines are thought to accelerate the humoral immune responses [3,4]. In normal condition, these type cytokines interact with each other to balance the ability of generating a vigorous response to provide defense against aggressors and protecting the body tissues from being damaged in immune responses [5,6]. The production of cytokine and expansion of cytokine-producing cells which are crucial for immune homeostasis are dominant by immune microenvironment.…”