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J Leukoc Biol. 2016 Nov;100(5):1125-1134. Epub 2016 Jun 10.

CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection.

Author information

1
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
2
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
3
Immunology Institute, Icahn School of Medicine, Mount Sinai, New York, New York, USA; and.
4
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; michelle-callegan@ouhsc.edu.
5
Dean McGee Eye Institute, Oklahoma City, Oklahoma, USA.

Abstract

During intraocular bacterial infections, the primary innate responders are neutrophils, which may cause bystander damage to the retina or perturb the clarity of the visual axis. We hypothesized that cytokine IL-6 and chemokine CXCL1 contributed to rapid neutrophil recruitment during Bacillus cereus endophthalmitis, a severe form of intraocular infection that is characterized by explosive inflammation and retinal damage that often leads to rapid vision loss. To test this hypothesis, we compared endophthalmitis pathogenesis in C57BL/6J, IL-6-/-, and CXCL1-/- mice. Bacterial growth in eyes of CXCL1-/-, IL-6-/-, and C67BL/6J mice was similar. Retinal function retention was greater in eyes of IL-6-/- and CXCL1-/- mice compared with that of C57BL/6J, despite these eyes having similar bacterial burdens. Neutrophil influx into eyes of CXCL1-/- mice was reduced to a greater degree compared with that of eyes of IL6-/- mice. Histology confirmed significantly less inflammation in eyes of CXCL1-/- mice, but similar degrees of inflammation in IL6-/- and C57BL/6J eyes. Because inflammation was reduced in eyes of infected CXCL1-/- mice, we tested the efficacy of anti-CXCL1 in B. cereus endophthalmitis. Retinal function was retained to a greater degree and there was less overall inflammation in eyes treated with anti-CXCL1, which suggested that anti-CXCL1 may have therapeutic efficacy in limiting inflammation during B. cereus endophthalmitis. Taken together, our results indicate that absence of IL-6 did not affect overall pathogenesis of endophthalmitis. In contrast, absence of CXCL1, in CXCL1-/- mice or after anti-CXCL1 treatment, led to an improved clinical outcome. Our findings suggest a potential benefit in targeting CXCL1 to control inflammation during B. cereus and perhaps other types of intraocular infections.

KEYWORDS:

Bacillus; chemokine; cytokine; eye endophthalmitis; mouse

PMID:
27286792
PMCID:
PMC5069095
DOI:
10.1189/jlb.3A0416-173R
[Indexed for MEDLINE]
Free PMC Article

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