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Activation of the Innate Immune System Is Augmented In Type 1 Diabetic Mice
Author(s) -
Lin KengI,
Johnson Daniel R.,
O’Connor Jason C.,
Freund Gregory G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a55-b
Subject(s) - innate immune system , lipopolysaccharide , streptozotocin , endocrinology , medicine , immune system , diabetes mellitus , type 2 diabetes , spleen , cytokine , proinflammatory cytokine , immunology , inflammation
We have previously shown that type 2 diabetes in the mouse is associated with increased responsivity to innate immune challenges [JI: 2005:174:4991, PNAS: 2005:102:15184]. Here we demonstrate that type 1 diabetes in mice induces a similar hyper‐responsivity to innate immune stimulation. Type 1 diabetes was induced in C57BL/6J‐ lepr db/+ mice with a single intraperitoneal (IP) injection of 200 mg/kg streptozotocin (STZ). After 3 d mice became hyperglycemic 399 ± 60 mg/dl and hypoinsulinemic 0.6 ± 0.1 ng/ml. To test for innate immune responsiveness, lipopolysaccharide (LPS) (100 μg/kg/mouse) was then administered IP and sickness response observed. At 2 h, STZ mice were 35 ± 5 % more sick than non‐diabetic controls. To examine the mechanism of enhanced LPS‐induced sickness, peritoneal fluid was examined for pro‐inflammatory cytokines. At 2 h post LPS, STZ mice showed a 4‐fold (IL‐1β) (p <0.02), 6‐fold (IL‐6) (p <0.001) and 3‐fold (TNF‐α) (p <0.05) increase in the indicated cytokines when compared to non‐STZ mice. In addition, post 2 h LPS‐dependent spleen expression of mRNA for the IL‐1 antagonist, IL‐1R2, was 10‐fold (p <0.4) lower in STZ mice. Taken together these findings indicate that response to innate immune challenge is augmented in the STZ mouse model of type 1 diabetes due to increased pro‐inflammatory cytokine production and reduced expression of the pro‐inflammatory counter‐regulator IL‐1R2.

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