The inflammatory reaction in autoimmune polymyositis and rejection of transplanted myoblasts is characterized by mononuclear cell infiltration. In other settings monocytes are locally recruited by an IL-6-induced IL-8-to-MCP-1 switch. IL-6, upon binding to soluble gp80 (sIL-6R), can interact with membrane-bound ubiquitously expressed gp130 and activate virtually all cells (transsignaling). We found that human myoblasts could use transsignaling to produce IL-6, MCP-1 and ICAM-1; the addition of sIL-6R, binding to IL-1beta-induced IL-6, greatly increases IL-6 production. These in vitro data support the hypothesis that locally secreted IL-6 can target monocyte chemotaxis and leukocytes trafficking through an IL-6, MCP-1 and ICAM-1 modulation.