Effects of intravitreal bevacizumab in Gram-positive and Gram-negative models of ocular inflammation

Autor: John Dickinson, Mark E. Seamone, Alan F. Cruess, R. Rishi Gupta, Melanie E. M. Kelly, James T. Toguri, J Daniel Lafreniere, Arif Samad, Daniel O'Brien
Rok vydání: 2018
Předmět:
0301 basic medicine
Lipopolysaccharides
Male
Vascular Endothelial Growth Factor A
Chemokine
Time Factors
genetic structures
Bevacizumab
Inflammation
Angiogenesis Inhibitors
Peptidoglycan
Pharmacology
Eye Infections
Bacterial
Uveitis
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Endophthalmitis
Medicine
Animals
Gram-Positive Bacterial Infections
Mice
Inbred BALB C
biology
business.industry
medicine.disease
eye diseases
3. Good health
Vascular endothelial growth factor
Ophthalmology
Vascular endothelial growth factor A
Disease Models
Animal
030104 developmental biology
chemistry
Intravitreal Injections
030221 ophthalmology & optometry
biology.protein
Cytokines
Tumor necrosis factor alpha
medicine.symptom
business
Gram-Negative Bacterial Infections
Intravital microscopy
medicine.drug
Zdroj: Clinicalexperimental ophthalmology. 47(5)
ISSN: 1442-9071
Popis: Background Exogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti-inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against vascular endothelial growth factor (VEGF), has anti-inflammatory properties in experimental models of Gram-positive and Gram-negative inflammation. Methods BALB/c mice were subjected to lipopolysaccharide- (LPS) or peptidoglycan- (PGN) induced ocular inflammation and treated with IVT bevacizumab. Iris microvasculature was imaged 6 hours following irritant/treatment using intravital microscopy (IVM) before the mice were euthanized and the eyes were enucleated immediately post-mortem. Following enucleation, levels of VEGF and 23 cytokines and chemokines (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, TNF, KC, G-CSF, GM-CSF, Eotaxin, INF-γ, MCP-1, MIP-1α, MIP-1β, RANTES) were quantified using a multiplex assay. Results Levels of VEGF were significantly increased during the inflammatory response, triggered by either PGN or LPS. Both the adherence of leukocytes to the iris vascular endothelium and the levels of pro-inflammatory cytokines and chemokines were significantly increased following administration of either irritant. Treatment with bevacizumab decreased levels of leukocyte adherence in LPS-treated eyes, however, not in PGN-treated eyes. Conversely, bevacizumab treatment decreased levels of cytokines and chemokines (TNF, IL-6, MCP-1, MIP-1α, MIP-1β, RANTES, KC) in PGN-treated eyes, however, not in LPS-treated eyes. Conclusions Within a 6-hour window bevacizumab had anti-inflammatory actions that were distinct in both Gram-positive (PIU) and Gram-negative (EIU) models, respectively. Given our findings, this would suggest that bevacizumab may have utility as an adjunctive therapy to IVT antibiotics and vitrectomy in the management of exogenous endophthalmitis.
Databáze: OpenAIRE
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