Intravitreally injected human immunoglobulin attenuates the effects of Staphylococcus aureus culture supernatant in a rabbit model of toxin-mediated endophthalmitis

Abstract

Objective: To determine whether human immunoglobulin attenuates the toxic effects of Staphylococcus aureus culture supernatant in a rabbit model of endophthalmitis.

Methods: Immunoglobulin binding to products of S aureus strain RN4220 was tested by Western blot analysis using known toxins (beta-hemolysin and toxic shock syndrome toxin-1) and a concentrated culture supernatant containing S aureus exotoxins (pooled toxin). To induce endophthalmitis, pooled toxin was injected into the rabbit vitreous. For immunoglobulin treatment, immunoglobulin and pooled toxin were either mixed and injected simultaneously or immunoglobulin was injected immediately after or 6 hours after pooled toxin injection. Severity of endophthalmitis was graded according to a 9-day course with clinical examination (slitlamp biomicroscopy or indirect ophthalmoscopy) and evaluation of histologic sections.

Results: The toxic effects of pooled toxin were markedly reduced when immunoglobulin was mixed with pooled toxin and injected simultaneously. Delayed injection of immunoglobulin diminished its ability to reduce toxicity. Clinical and histologic signs of toxicity were partially attenuated when immunoglobulin was injected immediately after pooled toxin, but only minimal clinically detectable reductions in toxicity were observed when immunoglobulin injection was delayed for 6 hours.

Conclusion: Pooled human immunoglobulin can attenuate the toxic intravitreal effects of a concentrated culture supernatant containing S aureus exotoxins. Clinical Relevance Immunoglobulin may represent a novel adjuvant in the treatment of bacterial endophthalmitis. To optimize the potential therapeutic benefit, maximizing the mixture of immunoglobulin with bacterial products and early intervention are likely to be important.