Interleukin 18 Contributes to Host Resistance and Gamma Interferon Production in Mice Infected with VirulentSalmonella typhimurium

Abstract

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-γ) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-γ-R−/− mice. IL-18 proved to be required for IFN-γ production by mouse splenocytes from conventional, scid, andrag-1 −/− mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-γ levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-γ.

Decreased interleukin-18 response in asthmatic children with severe Mycoplasma pneumoniae pneumonia

“…IL-18 has been demonstrated to have many biologic activities, including enhancement of Th1 cell activity and functional development of natural killer (NK) cells. IL-18 was reported to be produced during clinical and various animal models of infection and play a role in host defense against some microbial and fungal pathogens [15][16][17][18]. The role of IL-18 in the pathogenesis of bacterial pneumonia has also been studied.…”

Salmonella, the host and disease: a brief review

“…113 IL-18 contributes to IL-12 induced IFN-g in Salmonella infected mice and anti IL-18 treatment diminishes IFN-g levels in PP late in infection and survival time. 114,115 Cytokine and chemokine production may not only have beneficial but also pathological consequences for the host. Chemokines such as MCP-1, CCL2, CCL20 and CCL3 have protective roles in Salmonella infections (119, 120) but may also lead to tissue destruction by triggering a massive influx of inflammatory cells into infected organs.…”

Th1 and Th1-inducing cytokines inSalmonellainfection

“…The immune response to Salmonella infection has been studied extensively in mice [1][2][3]. IFN(interferon)-g and IFN-ginducing cytokines such as IL-12, IL-18 and IL-15 have been shown to play principal roles in the defence against murine Salmonella infection by studies using gene knockouts and cytokine neutralization [1][2][3][4][5][6][7]. IL-12 induces Th1 differentiation and IFN-g -production from Th1 cells, while IL-18 and IL-15 play synergistic roles with IL-12 as co-stimulants for optimal IFN-gproduction.…”