INCREASED IL-10 PRODUCTION BY STIMULATED WHOLE-BLOOD CULTURES IN PRIMARY IGA NEPHROPATHY

Most patients with primary IgA nephropathy (IgAN) have a significantly higher memory repertoire of IgA1-producing B lymphocytes in their bon e marrow together with high plasma levels of IgA1. The connection betw een the mucosal immune system and the bone marrow compartment is proba bly based on traffic of either antigen-presenting cells (APC) or antig en-specific lymphocytes. Cytokines play an important role in the proli feration and differentiation of lymphoid cells. In order to mimic the in vivo situation as much as possible, we assessed cytokine production profiles ex vivo in 23 IgAN patients and matched controls, using lipo polysaccharide (LPS)- or phytohaemagglutinin (PHA)-stimulated whole bl ood (WE) cultures. Interferon-gamma (IFN-gamma), IL-2, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha) production in culture supern atants were determined by cytokine-specific ELISAs. Compared with cont rols, PHA-stimulated cultures resulted in significantly higher IL-IO ( P<0.001), IL-2 (P < 0.005) and IFN-gamma (P < 0.001) levels in IgAN pa tients, but no significant differences in TNF-alpha or IL-6 levels wer e found. In LPS-stimulated cultures, the only significant difference ( P < 0.001) between the two groups was the increased IL-10 production i n IgAN patients. The enhanced cytokine production in stimulated WE cul tures suggests altered monocyte-related T cell responses in patients w ith IgAN. Increased IL-10 production may eventually result in an incre ased number of IgA-producing B lymphocytes in the bone marrow. In addi tion, high levels of endogenous IL-10 may down-regulate the effector f unctions of monocytes, or possibly APC in general, and consequently th e IgA response at the mucosal level.