Antibodies to Cytokine Protect Eyes During Bacterial Infection

Study shows improved pathology of bacterial eye infection upon topical treatment with polyclonal antibodies against the main neutrophil recruiting, proinflammatory cytokine; surprisingly, bacterial clearance was also improved.

Severe tissue damage during bacterial infections is often largely caused by inflammatory immune system by-products, noxious substances released from neutrophils attracted to the infection site to clear away the pathogen. As a key to attracting neutrophils, the proinflammatory cytokine interleukin-17 (IL-17) contributes to both microbial clearance as well as to inflammation-associated tissue damage.

A study led by researchers at Brigham and Women’s Hospital (Boston, MA, USA) investigated in vivo roles of IL-17 in mammalian eye infections using Pseudomonas aeruginosa to cause ulcerative keratitis after scratch injury in a mouse model. Two experimental approaches were used: examination of IL-17 receptor (IL-17R) deficient mice and testing of a topical treatment with polyclonal antibodies against IL-17. Pseudomonas aeruginosa was chosen mainly due to it being a common cause of corneal infections (particularly in those at higher risk such as extended-wear contact lens users) and as it is often found to be resistant to antibiotics.

The findings, published in the journal Infection and Immunity, October 2012, from both approaches showed that neutralization of IL-17 during P. aeruginosa corneal infection reduces neutrophil influx and pathology without compromising bacterial clearance. The antibody-mediated IL-17 neutralization approach was tested with six different laboratory or clinical P. aeruginosa strains, including both invasive and cytotoxic strains, all of which gave essentially the same results.

The strategy of inhibiting neutrophil tissue infiltration risked reducing the immune system’s bacteria-killing function - “We thought that blocking IL-17 infection might worsen eye infections,” said principal investigator Prof. Gregory P. Priebe of Brigham and Women’s Hospital and Boston Children’s Hospital, “Surprisingly, just the opposite was seen: blocking IL-17 with antibodies led both to fewer neutrophils in the eye, and to fewer bacteria.” The results therefore offer a new avenue for therapy of these sight-threatening infections.

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