Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Anti-Interleukin 23 Antibody Alleviates Nephritis in MRL/Lprlupus-Prone Mice.
Kampagianni, Ourania, Tsokos, George C., Kyttaris, Vasileios C.
Interleukin-23 (IL-23) dependent IL-17+ T helper lymphocytes (Th17) are potent inducers of tissue inflammation and have been associated with autoimmunity. We have previously shown the importance of IL-23/IL-17 axis in development of lupus nephritis and demonstrated that IL-23 receptor deficiency prevents the development of nephritis in lupus-prone mice. The aim of this study is to determine whether treatment of lupus-prone mice with an anti-IL-23 blocking antibody mitigates nephritis.
9-week old MRL/lpr lupus-prone mice were injected intraperitoneally three times a week with 20 mg of rat anti-mouse IL-23 antibody, or equal amount of rat anti-mouse IgG as control, for 7 weeks. Proteinuria was monitored by weekly urine collection. Serum samples were obtained at three different time points (start, middle and at the end of treatment). The mice (N=3 for each group) were subsequently sacrificed and spleen and lymph nodes were extracted for cell cultures, where cytokine production and gene expression were analyzed.
The anti-IL-23-treated mice (treated group) had significantly less proteinuria at the end of the study when compared to IgG treated (control group) (average albumin/creatinine ratio; treated: 4.1 mg/gr vs. control: 14.6 mg/gr). After 7 weeks, spleen and lymph nodes lymphocytes were activated in vitro with anti-CD3 and anti-CD28 antibodies; the supernatants were collected 24 hours later and tested for cytokine concentration. The anti-IL-23 antibody treatment decreased the production of IL-17A (treated: 208.6±69.1 pg/mL vs. control: 632.0±366.4 pg/mL) and IL-6 (treated: 427.8±114.7 pg/mL vs. control: 820.3±82.3 pg/mL). On the contrary IFNg did not differ between the groups.
Using targeted mRNA screening for inflammation related genes, we found that anti-IL-23 treatment resulted in a decrease by 79% of the levels of the chemokine receptor CCR2 in T cells, suggesting that IL-23 plays a significant role in lymphocyte trafficking in these mice.
Immunoglobulin and anti-dsDNA levels, which were already very high at the beginning of the treatment, did not change with this short anti-IL-23 treatment.
Treatment of lupus-prone mice with anti-IL-23 antibody leads to decreased production of Th17 related cytokines and amelioration of kidney disease. These results urge the development of IL-23 targeting therapeutic regimens in systemic lupus erythematosus patients.
To cite this abstract, please use the following information:
Kampagianni, Ourania, Tsokos, George C., Kyttaris, Vasileios C.; Anti-Interleukin 23 Antibody Alleviates Nephritis in MRL/Lprlupus-Prone Mice. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :563