Kidney and splanchnic handling of interleukin-6 in humans

Chronic elevation of circulating Interleukin-6 (IL-6) is observed in elderly individuals as well as in several illnesses, including chronic kidney diseases. A number of cells and tissues possess the ability to metabolize significant amounts of IL-6 in vitro. However, information on signals and mechanisms by which IL-6 is removed from blood in humans is still incomplete. To assess the individual role of splanchnic organs and kidney on IL-6 inter-organ exchange we used the IL-6 mass-balance technique across the hepato-splanchnic bed and kidney in six subjects with normal renal and liver function undergoing diagnostic venous catheterizations. Both in the hepatic and renal veins IL-6 levels were significantly lower (p=0.041 and 0.038, respectively), than in the artery. The fractional extraction of IL-6, i.e., the percentage of arterial IL-6 extracted after a single pass, was greater across the splanchnic organs (18%) than across the kidney (8%). Accordingly, IL-6 plasma clearance across splanchnic organs was greater than across the kidney and the sum of kidney and splanchnic removal accounted for as much as 63% of the estimated adipocyte IL-6 release. Our data demonstrate that, although the individual contribution to removal is different, both splanchnic organs and kidneys affect in a significant way the disposal of IL-6 in humans. According, both liver and kidney dysfunction could affect the handling of this proinflammatory cytokine and favour a chronic inflammatory response.