Rheumatoid arthritis (RA) is a chronic destructive
autoimmune disease characterised by periods of flare and remission. Today's treatment is based on continuous immunosuppression irrespective of the patient's inflammatory status. When the disease is in remission the
therapy is withdrawn but withdrawal attempts often results in inflammatory flares, and re-start of the
therapy is commenced when the
inflammation again is prominent which leads both to suffering and increased risk of tissue destruction. An attractive alternative treatment would provide a disease-regulated
therapy that offers increased anti-inflammatory effect during flares and is inactive during periods of remission. To explore this concept we expressed the immunoregulatory
cytokine interleukin (IL)-10 gene under the control of an
inflammation dependent promoter in a mouse model of RA -
collagen type II (CII) induced
arthritis (CIA). Haematopoetic stem cells (HSCs) were transduced with lentiviral particles encoding the
IL-10 gene (LNT-IL-10), or a green fluorescence
protein (GFP) as control gene (LNT-GFP), driven by the
inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after
transplantation of transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice developed a reduced severity of
arthritis compared to controls. The LNT-IL-10 mice exhibited both increased
mRNA expression levels of
IL-10 as well as increased amount of
IL-10 produced by B cells and non-B APCs locally in the lymph nodes compared to controls. These findings were accompanied by increased
mRNA expression of the
IL-10 induced suppressor of
cytokine signalling 1 (SOCS1) in lymph nodes and a decrease in the
serum protein levels of
IL-6. We also found a decrease in both frequency and number of B cells and serum levels of anti-CII
antibodies. Thus,
inflammation-dependent
IL-10 therapy suppresses experimental autoimmune
arthritis and is a promising candidate in the development of novel treatments for RA.