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

: 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‐γ, 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‐γ 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.