Role of Interleukin-6 Mediated T Cell Activation in Experimental Acute Pancreatitis

Acute pancreatitis (AP) is an inflammatory disease characterized by a prominent local infiltration and activation of innate immune cells, but also accompanied by a systemic T cell activation. The mechanisms which link the local immune response to the systemic immune activation are not well understood. Here, we identified Interleukin-6 (IL-6) as a crucial mediator of systemic T cell activation, which is mainly released by pancreatic macrophages and necrotic acinar cells. IL-6 triggers the systemic T cell activation of CD4+ T helper cells. After the onset of acute pancreatitis IL-6 serum levels increase rapidly and affect the systemic immune reaction. A CD4+ specific knock out of the IL-6 receptor glycoprotein 130 receptor (GP130R), showed reduced proliferation and a higher apoptosis rate of T cells after induction of caerulein-induced AP. This diminished T cell activation results in a significant decrease of pancreatic macrophage proliferation and a milder disease course. Our data indicate a critical role of IL-6 in the crosstalk between local and systemic immune responses during AP, as well as a triggering role in adaptive immune mechanisms.