<i>Salmonella</i> septicemia in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Association with decreased interferon‐γ production and toll‐like receptor 4 expression

Netea, Mihai G.; Radstake, Timothy; Joosten, Leo A. B.; Meer, J.W.M. van der; Barrera, Pilar; Kullberg, Bart Jan

doi:10.1002/art.11151

Cited by 106 publications

(43 citation statements)

References 15 publications

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“…Furthermore, innate immune functions via TLR4 might perpetuate inflammatory mechanisms and bypass the need for IL-1 in chronic joint inflammation (31). TNF-blocking treatment ex vivo significantly inhibited TLR4 expression on dendritic cells from RA patients (34). Therefore, it is conceivable that sST2 inhibits CIA through its down-regulation of TLR4 and TLR1.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

Leung

Culshaw

et al. 2004

The Journal of Immunology

160

125

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Rheumatoid arthritis is characterized by chronic inflammatory infiltration of the synovium, leading to eventual cartilage and bone destruction. Previously, we have reported that soluble T1/ST2 (sST2), a member of the IL-1R gene family, inhibits LPS-induced macrophage proinflammatory cytokine production. In this study, we report the therapeutic effect of sST2-Fc in the murine model of collagen-induced arthritis. A short term administration of sST2-Fc fusion protein significantly attenuated disease severity compared with controls treated with normal IgG. Histological examination revealed that while control IgG-treated mice developed severe cellular infiltration in the joints, synovial hyperplasia, and joint erosion, this pathology was profoundly reduced in sST2-Fc-treated animals. Treatment of sST2-Fc also down-regulated serum levels of IL-6, IL-12, and TNF-α. Spleen cells from the sST2-Fc-treated mice produced significantly less IFN-γ, TNF-α, IL-6, and IL-12 compared with cells from the control mice when cultured with collagen in vitro. Finally, pretreatment with ST2-Fc markedly inhibited the ability of human monocytic THP1 cells to release TNF-α when cocultured with peripheral blood T cells from rheumatoid patients. Together these results demonstrate that sST2-Fc may provide a novel approach in treating chronic autoimmune conditions by inhibiting the release of proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

“…The role of TLRs in RA has now been consistently demonstrated (31)(32)(33)(34)(35). For example, the TLR2 signaling pathways have been reported to contribute to the pathogenesis of RA (32,33), and is required for streptococcal cell wall-induced joint inflammation in mice (35).…”

Section: Discussionmentioning

confidence: 99%

A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

Leung

Culshaw

et al. 2004

The Journal of Immunology

160

125

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“…However, the down-regulation of TLRs, and especially TLR-2, which declines to levels below those found in healthy controls, might also interfere with normal host defense. In RA, the increased susceptibility to infections with essentially intracellular pathogens during TNF␣ blockade treatment has previously been related to decreased TLR-4 expression and interferon-␥ production by myeloid cells (40,41). The present in vivo data and our recent finding of tuberculosis reactivation and abscesses with streptococci in infliximab-treated SpA patients (37)(38)(39) are compatible with the hypothesis that TNF␣ blockade in vivo interferes with the normal innate immune response to pathogens and suggest that this might even be more pronounced in SpA than in RA.…”

Section: De Rycke Et Almentioning

confidence: 99%

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Rycke¹,

Vandooren²,

Kruithof³

et al. 2005

Arthritis & Rheumatism

120

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Results. Expression of TLR-4, but not TLR-2, was increased on PBMCs from patients with SpA, whereas both TLRs were increased in RA patients. TLR expression was particularly increased on the CD163؉ macrophage subset. Infliximab reduced TLR-2 and TLR-4 expression on monocytes of SpA and RA patients, leading to lower levels than in controls and to impaired TNF␣ production upon LPS stimulation. In inflamed synovium, the expression of both TLRs and of CD163 was significantly higher in patients with SpA than in those with RA or OA. Paralleling the systemic effect, TLRs in synovium were down-regulated following treatment with infliximab as well as etanercept, indicating a class effect of TNF␣ blockers.Conclusion. Inflammation in SpA is characterized by increased TLR-2 and TLR-4 expression, which is sharply reduced by TNF␣ blockade. These findings suggest a potential role of innate immunity-mediated inflammation in SpA and provide an additional clue regarding the mechanism of action as well as the potential side effects of TNF␣ blockade.

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“…TNF blockade ex vivo inhibits expression of Toll-like receptor 4 (TLR-4) on dendritic cells from RA patients and controls, 6 which has important implications with regard to susceptibility to multiple infectious organisms. LTA shares many of the same biological and structural characteristics of TNF, and their genes lie in tandem in the human MHC region on chromosome 6p21.…”

Section: Introductionmentioning

confidence: 99%

Genetic risk factors for infection in patients with early rheumatoid arthritis

et al. 2004

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We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis (RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): (TNF À308, À238, and þ 488); lymphotoxin-a (LTA) (LTA þ 249, þ 365, and þ 720); and Fc gamma receptors FCGR2A 131 H/R; FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P ¼ 0.038). Urinary tract infection (UTI) was associated with the TNF À238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05-6.25) and LTA þ 365 C (OR 1.73, 95% CI 1.07-2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99-3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (Po0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.

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Salmonella septicemia in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Association with decreased interferon‐γ production and toll‐like receptor 4 expression

Cited by 106 publications

References 15 publications

A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Genetic risk factors for infection in patients with early rheumatoid arthritis

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