Cytokine network in autoimmune haemolytic anaemia: new probable targets for therapy

Several immunological mechanisms seems to be similar in cancer and autoimmune disease. Studying interleukins production and proliferative response in autoimmune haemolytic anaemia (AIHA), it is possible to observe that manipulation of IL-10/IL-12 balance can have profound effect on the incidence of autoimmune diseases and this might be useful for the control of AIHA.

Respective role of IL-2, IL-4, IFN-gamma, IL-10 and IL-12 in non-cancer associated AIHA were investigated by examining the spontaneous and mitogen-induced (OKT3 or LPS) synthesis of these cytokines in PBMC cultures by ELISA methods.

Our results affirmed that AIHA is a disease which exhibited an increased basal synthesis of IL-4 and decreased levels of IFN-gamma by AIHA PBMC compared with controls and then there is a basal increase of Th2 cytokines. Th1-type cytokine decrease in basal state occurred in parallel with an increase of constitutive IL-10 production and a IL-12 decrease.

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 then the neutralisation 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 over B cell activation associated with AIHA and sometimes with cancer.