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-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.
Toriani-Terenzi
Caterina
C
Laboratory of Immunohematology, Catholic University Sacro Cuore, Viale dei Promontori 438, 00122 Rome, Italy. cttoriani@tiscali.it
Fagiolo
Enzo
E
D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology* / Q000276:immunology; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation
D001324:Autoantigens; D016207:Cytokines; D016753:Interleukin-10