title: Acute hyperglycemia impairs IL-6 expression in humans.
abstract: Normal glucose metabolism is critical to immune function but the effects of short-term hyperglycemia on immunity are not well described. To study this phenomenon, we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose and octreotide. An RNA-seq analysis of whole blood RNA demonstrated alterations in multiple immune pathways and transcripts during acute hyperglycemia including decreased transcription of IL-6, an important component of both innate and adaptive immune responses. Additional in vitro studies of human peripheral blood mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL-6 expression, most prominently in CD14(+)CD16(+) intermediate monocytes. Hyperglycemia also reduced IL-17A expression suggesting further impairment of immune responses during acute hyperglycemia. These findings demonstrate multiple defective immune responses in acute hyperglycemia and suggest a novel role for intermediate monocytes as metabolically sensitive innate immune cells.
authors.affiliation: The Diabetes Center UCSF School of Medicine San Francicsco California 94143 USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Spindler
authors.affiliation: The Diabetes Center UCSF School of Medicine San Francicsco California 94143 USA.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Ho
authors.affiliation: The Diabetes Research Program Benaroya Research Institute Seattle Washington 98040 USA.
authors.forename: David
authors.initials: D
authors.lastname: Tridgell
authors.affiliation: The Diabetes Research Program Benaroya Research Institute Seattle Washington 98040 USA.
authors.forename: Marli
authors.initials: M
authors.lastname: McCulloch-Olson
authors.affiliation: The Diabetes Research Program Benaroya Research Institute Seattle Washington 98040 USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gersuk
authors.affiliation: The Diabetes Research Program Benaroya Research Institute Seattle Washington 98040 USA.
authors.forename: Chester
authors.initials: C
authors.lastname: Ni
authors.affiliation: The Diabetes Research Program Benaroya Research Institute Seattle Washington 98040 USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Greenbaum
authors.affiliation: The Diabetes Center UCSF School of Medicine San Francicsco California 94143 USA.
authors.forename: Srinath
authors.initials: S
authors.lastname: Sanda
keywords: Hyperglycemia; IL‐17; IL‐6; metabolism; monocyte