Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1997 Jan 15;89(2):577-82.

The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice

M G Netea  1 , B J Kullberg, W L Blok, R T Netea, J W van der Meer
Affiliations
  • PMID: 9002961
Free article

The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice

M G Netea et al. Blood. .
Free article

Abstract

Patients with severe granulocytopenia are more susceptible to severe infections and sepsis. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF), interleukin-1 alpha (IL-1 alpha), and IL-1 beta play an important role in the pathophysiology of sepsis. The profile of these proinflammatory cytokines after lipopolysaccharide (LPS) challenge in cyclophosphamide-induced neutropenic mice was assessed, and possible mechanisms responsible for the modified cytokine production were studied. After LPS, both circulating concentrations of TNF and IL-1 alpha in neutropenic mice were 50% to 200% higher than those of controls, whereas IL-1 beta concentrations were not modified. The kinetics of cytokine production were similar in neutropenic and control animals. The susceptibility of neutropenic mice to an LPS challenge was increased. The observed overproduction of TNF and IL-1 alpha was not due to a direct effect of cyclophosphamide treatment. Because circulating concentrations of uric acid were increased in the neutropenic mice, the effect of hypouricemic treatment with allopurinol and sodium bicarbonate was investigated; such treatment in neutropenic mice challenged with LPS was followed by an improved survival and a reduced proinflammatory cytokine production towards the concentrations in control mice. Hyperuricemia induced by repeated administrations of uric acid in normal mice led to an increased TNF production after LPS. In conclusion, neutropenic mice respond with enhanced cytokine production and increased susceptibility to an LPS challenge, and hyperuricemia probably plays an important role in this phenomenon.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

LinkOut - more resources