Enhancement of neutrophil function by interleukin-18 therapy protects burn-injured mice from methicillin-resistant Staphylococcus aureus.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a grave concern in burn-injured patients. We investigated the efficacy of interleukin-18 (IL-18) treatment in postburn MRSA infection. Alternate-day injections of IL-18 into burn-injured C57BL/6 mice significantly increased their survival after MRSA infection and after methicillin-sensitive S. aureus infection. Although IL-18 treatment of burn-injured mice augmented natural IgM production before MRSA infection and gamma interferon (IFN-γ) production after MRSA infection, neither IgM nor IFN-γ significantly contributed to the improvement in mouse survival. IL-18 treatment increased/restored the serum tumor necrosis factor (TNF), IL-17, IL-23, granulocyte colony-stimulating factor (G-CSF), and macrophage inflammatory protein (MIP-2) levels, as well as the neutrophil count, after MRSA infection of burn-injured mice; it also improved impaired neutrophil functions, phagocytic activity, production of reactive oxygen species, and MRSA-killing activity. However, IL-18 treatment was ineffective against MRSA infection in both burn- and sham-injured neutropenic mice. Enhancement of neutrophil functions by IL-18 was also observed in vitro. Furthermore, when neutrophils from IL-18-treated burn-injured mice were adoptively transferred into nontreated burn-injured mice 2 days after MRSA challenge, survival of the recipient mice increased. NOD-SCID mice that have functionally intact neutrophils and macrophages (but not T, B, or NK cells) were substantially resistant to MRSA infection. IL-18 treatment increased the survival of NOD-SCID mice after burn injury and MRSA infection. An adoptive transfer of neutrophils using NOD-SCID mice also showed a beneficial effect of IL-18-activated neutrophils, similar to that seen in C57BL/6 mice. Thus, although neutrophil functions were impaired in burn-injured mice, IL-18 therapy markedly activated neutrophil functions, thereby increasing survival from postburn MRSA infection.

• Authors: Manabu Kinoshita, Hiromi Miyazaki, Satoshi Ono, Akihito Inatsu, Hiroyuki Nakashima, Hironori Tsujimoto, Nariyoshi Shinomiya, Daizoh Saitoh, Shuhji Seki
• Journal: Infection and immunity (Infect Immun) Vol. 79 Issue 7 Pg. 2670-80 (Jul 2011) ISSN: 1098-5522 [Electronic] United States
• PMID: 21536791 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Immunoglobulin M
• Interleukin-18
• Interferon-gamma

Topics

• Adoptive Transfer
• Animals
• Burns (immunology, microbiology)
• Cytokines (blood)
• Immunoglobulin M (immunology)
• Interferon-gamma (immunology)
• Interleukin-18 (administration & dosage, immunology, therapeutic use)
• Male
• Methicillin-Resistant Staphylococcus aureus (immunology, pathogenicity)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, SCID
• Neutrophils (immunology)
• Phagocytosis (drug effects)
• Staphylococcal Skin Infections (drug therapy, immunology, microbiology)