title: Kidney and splanchnic handling of interleukin-6 in humans.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Genoa University, Genoa, Italy. gari@unige.it
authors.forename: Giacomo
authors.initials: G
authors.lastname: Garibotto
authors.forename: Antonella
authors.initials: A
authors.lastname: Sofia
authors.forename: Manrico
authors.initials: M
authors.lastname: Balbi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Procopio
authors.forename: Barbara
authors.initials: B
authors.lastname: Villaggio
authors.forename: Alice
authors.initials: A
authors.lastname: Tarroni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Martino
authors.forename: Valeria
authors.initials: V
authors.lastname: Cappelli
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Gandolfo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valli
authors.forename: Daniela
authors.initials: D
authors.lastname: Verzola
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013152:Splanchnic Circulation
chemical_list: D015850:Interleukin-6