Interleukin-10 (IL-10) augments allograft arterial disease - Paradoxical effects of IL-10 in vivo

Interleukin-10 (IL-10) is an anti-inflammatory helper T cell type 2 (Th2) c ytokine that modulates Th1-type cytokine production. Graft arterial disease (GAD) is a vascular obliterative process mediated via the Th1 cytokine int erferon-gamma (IFN-gamma); allografts in IFN-gamma-deficient animals do not develop GAD, We investigated the effect of IL-10 and anti-IL-10 on GAD in murine heart transplants and whether anti-IL-10 reestablishes GAD in IFN-ga mma-deficient hosts. Major histocompatibility complex class II-mismatched h earts were transplanted for 8 weeks into wild-type or IFN-gamma-deficient m ice. In one set of experiments, wild-type hosts received daily administrati on of phosphate-buffered saline (PBS) or increasing IL-10; in a subsequent set of experiments, wild-type hosts received weekly PBS, rat IgG, or anti-I L-10 monoclonal antibody; IFN-gamma-deficient recipients received weekly PB S or anti-IL-10 monoclonal antibody. Explanted allografts were assessed for parenchymal rejection and GAD, cytokine profiles, and adhesion/costimulato ry-molecule expression. Exogenous IL-10 resulted in increased Th2-like cyto kine production; nevertheless, it exacerbated parenchymal rejection and GAD and increased CD8(+) infiltration. Anti-IL-10 did not significantly affect the extent of rejection or GAD, cytokine profiles, or immunohistology of t he allografts in wild-type hosts. Adhesion molecule (CD54 and CD106) expres sion was not diminished by IL-10 treatment, and costimulatory-molecule (CD8 0 and CD86) expression was augmented by administration of exogenous IL-10. Allografts in IFN-gamma-deficient recipients showed mild refection and no G AD, regardless of anti-IL-10 treatment. IL-10 in vivo thus has markedly dif ferent effects than predicted from in vitro experience. Although allografts develop Th2-like cytokine profiles treatment with IL-10 causes exacerbated rejection and GAD.