Short-term IL-1beta blockade reduces monocyte CD11b integrin expression in an IL-8 dependent fashion in patients with type 1 diabetes.
OBJECTIVE
Interleukin 1-beta (IL-1beta) is a major inflammatory cytokine. Blockade of the IL-1beta pathway is therapeutically efficacious in type 2 diabetes, but the mechanistic effects on the immune system are incompletely understood.


METHODS
We administered an IL-1 receptor antagonist, anakinra, to 7 type 1 diabetes patients in order to investigate the immunologic and metabolic effects of this drug. Mechanistic assays were performed before and after drug administration.


RESULTS
A novel signature was observed, with reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression.


CONCLUSIONS
This set of linked phenotypes suggests that blockade of the IL-1beta pathway results in the reduced ability of mononuclear cells to traffic to sites of inflammation. Mechanistic studies from large scale trials using IL-1 blockade in type 1 diabetes should focus on changes in monocyte trafficking and the IL-8 pathway.
Sanda
Srinath
S
Benaroya Research Institute, Seattle, WA, USA. ssanda@benaroyaresearch.org
Bollyky
Jenna
J
Standifer
Nathan
N
Nepom
Gerald
G
Hamerman
Jessica A
JA
Greenbaum
Carla
C
D000293:Adolescent; D000328:Adult; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
D039481:CD11b Antigen; D007004:Hypoglycemic Agents; C509295:ITGAM protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D016209:Interleukin-8