Intravitreal human immune globulin in a rabbit model of Staphylococcus aureus toxin-mediated endophthalmitis: a potential adjunct in the treatment of endophthalmitis.
OBJECTIVE
To test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endophthalmitis, the ocular tolerance, distribution, and ability of intravitreal IG to attenuate the toxic effects of Staphylococcus aureus culture supernatant were evaluated in a rabbit model.


METHODS
Effects of intravitreally injected IG were assessed histologically and with Western blot analysis performed 1 to 5 days after injection. IG reactivity to products of S. aureus strain RN4220 was tested by Western blotting, using known toxins (beta hemolysin and toxic shock syndrome toxin-1) and a concentrated culture supernatant containing S. aureus exotoxins (pooled toxin, PT). Endophthalmitis was induced by intravitreal PT injection. For treatment, IG and PT were mixed and injected simultaneously, or IG was injected immediately after, or 6 hours after, PT injection. PT toxicity was graded clinically and histologically over 9 days.


RESULTS
IG persisted intravitreally at least 5 days, inducing no clinical inflammation and minimal mononuclear cell infiltration. In the endophthalmitis model, toxicity from PT was significantly reduced when IG was mixed with PT and injected simultaneously, or when IG was delivered immediately after PT. Only minimal clinically detectable reductions were observed when IG delivery was delayed 6 hours.


CONCLUSIONS
Intravitreal IG is well tolerated in the rabbit eye and attenuates the toxicity of culture supernatant containing S. aureus exotoxins. Because toxin elaboration likely occurs gradually in true infection, reduced effects observed with delayed treatment in this toxin-injected model do not preclude clinical application. IG may represent a novel adjunct in endophthalmitis treatment.
Han
Dennis P
DP
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
D000818:Animals; D001427:Bacterial Toxins; D004334:Drug Administration Schedule; D009877:Endophthalmitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005098:Exotoxins; D005240:Feasibility Studies; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007267:Injections; D011817:Rabbits; D013211:Staphylococcus aureus; D014822:Vitreous Body
D001427:Bacterial Toxins; D005098:Exotoxins; D007136:Immunoglobulins