Interleukin-32γ transgenic mice resist LPS-mediated septic shock.

Abstract

Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory cytokines such as TNFα, IL-1β, and IL-6 as well as chemokines. There are five splicing variants (α, β, γ, delta, and epsilon) and IL-32γ is the most active isoform. We generated human IL-32γ transgenic (IL-32γ TG) mice to express high level of IL-32γ in various tissues, including immune cells. The pathology of sepsis is based on the systemic inflammatory response that is characterized by upregulating inflammatory cytokines in whole body, particularly in response to gram-negative bacteria. We investigated the role of IL-32γ in a mouse model of experimental sepsis by using lipopolysaccharides (LPS). We found that IL-32γTG mice resisted LPS-induced lethal endotoxemia. IL-32γ reduced systemic cytokines release after LPS administration but not the local immune response. IL-32γTG increased neutrophil influx into the initial foci of the primary injected site, and prolonged local cytokines and chemokines production. These results suggest that neutrophil recruitment in IL-32γTG occurred as a result of the local induction of chemokines but not the systemic inflammatory cytokine circulation. Together, our results suggest that IL-32γ enhances an innate immune response against local infection but inhibits the spread of immune responses, leading to systemic immune disorder.

• Authors: Sun Jong Kim, Siyoung Lee, Areum Kwak, Eunsom Kim, Seunghyun Jo, Suyoung Bae, Youngmin Lee, Soyoon Ryoo, Jida Choi, Soohyun Kim
• Journal: Journal of microbiology and biotechnology (J Microbiol Biotechnol) Vol. 24 Issue 8 Pg. 1133-42 (Aug 2014) ISSN: 1738-8872 [Electronic] Korea (South)
• PMID: 24743568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL32 protein, human
• Interleukins
• Lipopolysaccharides

Topics

• Animals
• Disease Models, Animal
• Disease Resistance
• Gene Expression
• Humans
• Interleukins (genetics, metabolism)
• Lipopolysaccharides (administration & dosage, toxicity)
• Mice
• Mice, Transgenic
• Shock, Septic (chemically induced, immunology, prevention & control)
• Systemic Inflammatory Response Syndrome (chemically induced, immunology, prevention & control)