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Skin disease is prevented but nephritis is accelerated by multiple pregnancies in autoimmune MRL/LPR mice

Department of Pathophysiology, Semmelweis University, Budapest, Hungary

M. Godó

Department of Pathophysiology, Semmelweis University, Budapest, Hungary

E. Nagy

Central Immunological Laboratory, Semmelweis University, Budapest, Hungary

M. Kardos

2nd Department of Pathology, Semmelweis University, Budapest, Hungary

K. Kotsch

Institute of Medical Immunology, Medical University Berlin Charité, Berlin, Germany

P. Casalis

Department of Neurosurgery, Medical University Berlin Charité, Berlin, Germany

C. Bodor

Department of Pathophysiology, Semmelweis University, Budapest, Hungary

L. Rosivall

Department of Pathophysiology, Semmelweis University, Budapest, Hungary

H-D. Volk

Institute of Medical Immunology, Medical University Berlin Charité, Berlin, Germany

A.C. Zenclussen

Institute of Medical Immunology, Medical University Berlin Charité, Berlin, Germany

P. Hamar

Department of Pathophysiology, Semmelweis University, Budapest, Hungary, hampet{at}net.sote.hu

The role of pregnancy in the progression of systemic lupus erythematosus (SLE) is still poorly understood. We analysed the effect of repeated pregnancies in MRL/lpr mice, a murine model of SLE. Seven-week old female mice were used: multiparous mice underwent three consecutive pregnancies (M); age-matched virgin mice served as controls (V). Animals were harvested at 20 weeks of age. Skin lesions were characterized by hair loss and scabs in the dorsum of the neck. Virgin skins showed thickened dermis, fibrosis and mononuclear cell infiltrates, which were practically absent in M. This was accompanied by higher IFN- and lower IL-10 mRNA expression levels in V compared to M skin. Plasma IFN- protein levels were also upregulated in V versus M. However, survival and kidney function were dramatically reduced and accompanied by hypertension after multiple pregnancies. Kidney histology also showed markedly increased renal lesions in M. In contrast to plasma and skin levels, both IL-10 and IFN- mRNA were lower in the kidneys of V versus M mice. Concluding our findings, the pathomechanisms of lupus kidney and skin disease may be regulated differently at the organ level during pregnancy. Both IFN- and IL-10 may be important regulatory cytokines at the local level. Lupus (2007) 16, 465—477.

Key Words: cytokines • kidney • mouse • skin • systemic lupus erythematosus

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