Intravitreally Injected Human Immunoglobulin Attenuates the Effects of Staphylococcus aureus Culture Supernatant in a Rabbit Model of Toxin-Mediated Endophthalmitis

Objective To determine whether human immunoglobulin attenuates the toxic effectsof Staphylococcus aureus culture supernatant in arabbit model of endophthalmitis. Methods Immunoglobulin binding to products of S aureus strainRN4220 was tested by Western blot analysis using known toxins (β-hemolysinand 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 simultaneouslyor immunoglobulin was injected immediately after or 6 hours after pooled toxininjection. Severity of endophthalmitis was graded according to a 9-day coursewith clinical examination (slitlamp biomicroscopy or indirect ophthalmoscopy)and evaluation of histologic sections. Results The toxic effects of pooled toxin were markedly reduced when immunoglobulinwas mixed with pooled toxin and injected simultaneously. Delayed injectionof immunoglobulin diminished its ability to reduce toxicity. Clinical andhistologic signs of toxicity were partially attenuated when immunoglobulinwas injected immediately after pooled toxin, but only minimal clinically detectablereductions in toxicity were observed when immunoglobulin injection was delayedfor 6 hours. Conclusion Pooled human immunoglobulin can attenuate the toxic intravitreal effectsof a concentrated culture supernatant containing S aureus exotoxins. Clinical Relevance Immunoglobulin may represent a novel adjuvant in the treatment of bacterialendophthalmitis. To optimize the potential therapeutic benefit, maximizingthe mixture of immunoglobulin with bacterial products and early interventionare likely to be important.