Treatment of corneal transplant rejection in humans with anti-interferon-γ antibodies

Skurkovich, S. V.; Kasparov, Alexander; Narbut, N P; Skurkovich, Boris

doi:10.1016/s0002-9394(02)01433-2

Cited by 17 publications

(9 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many human viruses, such as severe acute respiratory syndrome, EBV, varicella-zoster, and the 1918 or 2010 H1N1 IAV strains (which can result in lung pathology similar to our heterologous infection mouse model) (13,14), cause much more severe disease in young healthy adults, who have large complex memory populations, than in young children (46)(47)(48). Short-term appropriately timed anti-IFN-g treatment, which is available (49,50), may be useful in these kinds of circumstances.…”

Section: Discussionmentioning

confidence: 99%

Anti–IFN-γ and Peptide-Tolerization Therapies Inhibit Acute Lung Injury Induced by Cross-Reactive Influenza A–Specific Memory T Cells

Wlodarczyk

Kraft²,

Chen³

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Viral infections have variable outcomes with severe disease occurring in only few individuals. We hypothesized that this variable outcome could correlate with the nature of responses made to previous microbes. To test this, mice were infected initially with IAV and in memory-phase challenged with LCMV, which we show here to have relatively minor cross-reactivity with IAV. The outcome in genetically identical mice varied from mild pneumonitis to severe acute lung injury with extensive pneumonia and bronchiolization, similar to that observed in patients that died of the 1918 H1N1 pandemic. Lesion expression did not correlate with virus titers. Instead, disease severity directly correlated with and was predicted by the frequency of IAV-PB1703- and -PA224-specific responses, which crossreacted with LCMV-GP34 and -GP276, respectively. Eradication or functional ablation of these pathogenic memory T-cell populations, using mutant-viral strains, peptide-based tolerization strategies, or short-term anti-IFNγ treatment inhibited severe lesions such as bronchiolization from occurring. Heterologous immunity can shape outcome of infections and likely individual responses to vaccination, and can be manipulated to treat or prevent severe pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti–IFN-γ and Peptide-Tolerization Therapies Inhibit Acute Lung Injury Induced by Cross-Reactive Influenza A–Specific Memory T Cells

Wlodarczyk

Kraft²,

Chen³

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…An anti‐human IFNγ antibody (fontolizumab) has been shown to be safe in clinical trials in Crohn's disease (Hommes et al, 2006; Reinisch et al, 2006). In addition, fontolizumab's therapeutic effects have been documented in patients with inflammatory skin diseases and in a clinical trial of patients with corneal transplant rejection (Skurkovich et al, 2002; Skurkovich & Skurkovich, 2005). The patient numbers might not be large enough to draw any firm conclusions on any infectious, neoplastic and allergic complications potentially attributable to fontolizumab.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of IFNγ defeats haemophagocytosis in LCMV‐infected perforin‐ and Rab27a‐deficient mice

et al. 2009

View full text Add to dashboard Cite

Hereditary haemophagocytic lymphohistiocytosis (HLH) is a fatal inflammatory disease and treatments currently may lead to serious side effects. There is a pressing need for effective, less toxic treatments for this disease. Previous reports have suggested that interferon γ (IFNγ) has a role in the pathogenesis of HLH. Here, we report that blocking IFNγ had a therapeutic effect in two different murine models of human hereditary HLH (perforin-deficient and Rab27a-deficient mice, both infected with lymphocytic choriomeningitis virus). Therapeutic administration of an anti-IFNγ antibody induced recovery from haemophagocytosis in both genetic models, as evidenced by increased survival in perforin-deficient mice and correction of blood cytopenia, moderation of body temperature changes, decreased cytokinaemia, restoration of splenic architecture and reduced haemophagocytosis in the liver of both murine models. Involvement of the central nervous system in Rab27a-deficient mice was prevented by anti-IFNγ therapy. Hepatic T-cell infiltrates and virus persisted, with no detectable harm during the time course of these studies. These data strongly suggest that neutralization of IFNγ could be used in humans to safely alleviate the clinical manifestations of haemophagocytosis.

show abstract

“…IL-10 has been shown to decrease the expression of MHC class II in monocytes/macrophages, and therefore interfering with their antigen-presenting function. In addition, IL-10 modulates monocytes by suppressing the production of their proinflammatory cytokines, such as TNF-α, IL-1β and IL-8 [34] . In our study, the fact that IL-10 concentration suddenly decreased at the onset of corneal rejection suggests a loss of protection by this cytokine.…”

Section: Discussionmentioning

confidence: 99%

Impact of a Case Series of Corneal Transplant Rejection on the Kinetics of Cytokine Concentrations in Human Tears after Keratoplasty

Fuchigami

Huang²,

Nakajima³

et al. 2015

International Journal of Ophthalmic Research

View full text Add to dashboard Cite

Treatment of corneal transplant rejection in humans with anti-interferon-γ antibodies

Cited by 17 publications

References 4 publications

Anti–IFN-γ and Peptide-Tolerization Therapies Inhibit Acute Lung Injury Induced by Cross-Reactive Influenza A–Specific Memory T Cells

Anti–IFN-γ and Peptide-Tolerization Therapies Inhibit Acute Lung Injury Induced by Cross-Reactive Influenza A–Specific Memory T Cells

Neutralization of IFNγ defeats haemophagocytosis in LCMV‐infected perforin‐ and Rab27a‐deficient mice

Impact of a Case Series of Corneal Transplant Rejection on the Kinetics of Cytokine Concentrations in Human Tears after Keratoplasty

Contact Info

Product

Resources

About