Cytokine imbalance in NZB/W mice is associated with autoantibody levels and nephritis

Background

In the NZB/W murine model of lupus, various studies have analyzed cytokine production during disease development with contradictory results.

Objective

The aim of this study was to analyze cytokine pattern of splenic T cells from NZB/W mice. We assessed the possibility that a shift in cytokine production is associated with age, disease activity, or manifestation of nephritis.

Methods

NZB/W mice of different ages spanning 5–36 weeks were analyzed, and healthy (BALB/c × NZW) F1 mice were used as controls. Proteinuria was measured using albustix. Plasma creatinine and autoantibody levels were detected by commercial test kid and by ELISA, respectively. Splenic CD4⁺ T cells stimulated with PMA/Ionomycin were analyzed for intracellular cytokine staining by FACS analysis.

Results

The increased frequency of IFN-γ producing CD4⁺ T cells correlated with age, anti-dsDNA IgG antibody levels and proteinuria. The increasing number of IL-10 producers was only associated with anti-dsDNA antibody levels and proteinuria. A small gain in IL-4⁺ T cells correlated with plasma creatinine. Neither the number of IL-10 nor that of IL-4 exhibiting T cells correlated with age. There was no significant change observed in the production of TNF-α. Calculating the IFN-γ/IL-4 ratio, an increasing shift toward a Th1 response was observed. The shift strongly correlated with anti-dsDNA antibody titres and proteinuria. In contrast, no cytokine shift could be observed in control mice with increasing age.