臨床病理学ジャーナル

抽象的な

Biological Features of IL-12 and IFN-�?³ in the Pathogenesis of Systematic Lupus Erythematosus

Bin Wang, Jin-Sen Lu and Zhi-Hui Wang

Systemic lupus erythematosus is a chronic autoimmune disease characterized by abnormal immune response with overproduction of auto-antibodies, self-destructive complexes and hyperactivity of both T and B lymphocytes. Although the exact pathogenesis of SLE remains unclear, it has been found that the imbalance of Th1/Th2, subsequent cytokines and anti- or pro-inflammatory mediators could reflect the stage and phenotype of SLE. Among diverse cytokines involved in the disease progression, IL-12 and IFN-γ gain much attention for their biological functions in SLE. There existed many divergences on the expression levels of IL-12 while few conflicts were demonstrated on elevated levels of IFN-γ in SLE patients. By analysis of gene polymorphisms, it was suggested that positive correlations were observed between IL-12B rs3212227, IL-12B rs17860508 and susceptibility to and severity of SLE in Polish patients. In addition, the combination of the IL-12B rs17860508 GC allele and/or IL-12B rs3212227 C allele could increase the risk of SLE progression and/or severity of SLE parameters in Polish population. Furthermore, it was also found that the incorporation of IFN-γ R1 Met 14/Val 14 and IFN-γ R2 Gln 64/Gln 64 genotypes was a potential risk factor for SLE. Based on the precious researches, IL-12 and IFN-γ targeted gene therapy was developed and found to be effective in murine lupus. Intramuscular injection of IFN-γR/IgG1Fc fusion protein encoded cDNA and suppressive ODN was found to decrease the severity of disease and promote survival of lupus mice. On the other hand, intramuscular injection of IL-12 and IL-18 encoded plasmids alone or together was also observed to have therapeutic effects on murine lupus. All in all, this review mainly introduces the biological features and the potential therapeutic effects of IL-12 and IFN-γ in the pathogenesis of SLE.