Role of interleukin‐18 in experimental group B streptococcal arthritis

Tissi, Luciana; McRae, Bradford L.; Ghayur, Tariq; Hunolstein, Christina von; Orefici, Graziella; Bistoni, Francesco; Puliti, Manuela

doi:10.1002/art.20014

Cited by 14 publications

(10 citation statements)

References 47 publications

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“…In synergy with IL-23, IL-18 activates Th17 cells to produce IL-17. IL-18 inhibition reduces IL-1␤, IL-6, MIP-1 and MIP-2 in streptococcal arthritis (38) and reduces MCP-1 production in macrophages (44). Of the multiple cytokines/chemokines increased in the kidney in AKI, CXCL1 was the only cytokine that was reduced in the kidney in the IL-18 BP Tg mice.…”

Section: Discussionmentioning

confidence: 97%

Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury

He¹,

Lu²,

Altmann³

et al. 2008

American Journal of Physiology-Renal Physiology

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IL-18 function is neutralized in IL-18 binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. IL-18BP Tg mice were functionally and histologically protected against ischemic AKI as determined by blood urea nitrogen, serum creatinine, and acute tubular necrosis score. We have demonstrated that the injurious effect of IL-18 in the kidney is independent of neutrophils and lymphocytes. Thus the effect of IL-18 inhibition on renal macrophage infiltration was determined. The number of macrophages was significantly reduced in IL-18BP Tg compared with wild-type kidneys. To determine the cytokines and chemokines that are dependent on IL-18, we performed flow cytometry based assays. Multiple chemokines/cytokines, IL-3, IL-6, IL-15, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, macrophage inflammatory protein-2, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1 were significantly increased in AKI vs. sham kidneys. Only CXCL1 (also known as KC or IL-8) was significantly increased in AKI vs. sham kidneys and significantly reduced in IL-18BP Tg AKI vs. wild-type AKI kidneys. To determine whether macrophages are the source of CXCL1 in the kidney, we depleted macrophages with liposomal encapsulated clodronate. CXCL1 was significantly decreased in macrophage-depleted vs. control AKI mice. In summary, in ischemic AKI in mice, 1) IL-18BP Tg mice are functionally and histologically protected, 2) macrophage infiltration in the kidney and CXCL1 are significantly reduced in IL-18BP Tg mice, and 3) macrophage depletion significantly reduces CXCL1 in the kidney. In conclusion, protection against ischemic AKI in IL-18BP Tg mice is associated with less macrophage infiltration and less production of CXCL1 in the kidney.

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Section: Discussionmentioning

confidence: 97%

Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury

He¹,

Lu²,

Altmann³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…IL-18 is expressed in the rheumatoid arthritis synovial membrane in macrophages, which correlates with TNF-␣ and IL-1␤ expression and disease severity (20). IL-18-deficient mice exhibit reduced incidence and severity of collagen-induced arthritis (5,30), and IL-18 neutralization ameliorates streptococcus-induced arthritis (41). Thus, IL-18 is an important molecule for the development of arthritis.…”

Section: Discussionmentioning

confidence: 99%

MyD88 Deficiency Results in Tissue-Specific Changes in Cytokine Induction and Inflammation in Interleukin-18-Independent Mice Infected withBorrelia burgdorferi

et al. 2006

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Toll-like receptors (TLRs) play an important role in the control of infection with Borrelia burgdorferi.Deficiencies in TLR-2 or the shared TLR adapter molecule MyD88 have been shown to result in greatly increased bacterial burdens in mice. However, although in vitro studies have shown that the activation of TLR pathways by B. burgdorferi results in the release of inflammatory cytokines, studies in deficient mice have shown either no change or increased rather than decreased inflammation in infected animals. In this study, we looked at mechanisms to explain the increase in inflammation in the absence of MyD88. We found that MyD88-deficient mice infected with B. burgdorferi did not show increased inflammation at sites typically associated with Lyme disease (joints and heart). However, there was markedly increased inflammation in the muscles, kidneys, pancreas, and lungs of deficient animals. Muscle inflammation was typically seen perivascularly and perineuronally similar to that seen in infected humans. Chemotactic chemokines and cytokines were greatly increased in the muscle and kidneys of MyD88-deficient animals but not in the joints or heart tissue, suggesting that MyD88-independent pathways for recognizing B. burgdorferi and inducing these chemokines are present in the muscle and kidneys. Interleukin-18 signaling through MyD88 does not appear to play a role in either control of infection or inflammation.

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“…Potential targets include constituents of the bacterial cell wall, molecules involved in bacterial adhesion and oligonucleotide sequences in bacterial DNA [29][30][31]. In addition the genetic deletion of cell-derived cytokines, using the creation of knockout mice, have been shown to be an elegant way of elucidating the roles of multiple components of the immune system in the host response to bacterial infection [32][33][34][35][36][37][38].…”

Section: Future Management Of Septic Arthritismentioning

confidence: 99%