Hemoglobin exacerbates the ocular inflammatory response to endotoxin.
BACKGROUND
There is a clinical impression that bleeding into sites of inflammation exacerbates the inflammatory response. It has been hypothesized that hemoglobinic iron (Fe) contributes to this response by catalyzing free radical reactions. In the present study, the effects of autologous hemoglobin on the inflammatory response to endotoxin was determined. In addition, the possible contributions of Fe to this response was assessed by co-injection of either transferrin or desferrioxamine.


METHODS
A mild ocular inflammation was induced in rabbits by intravitreal injection of 0.25 ng endotoxin. In some animals apotransferrin, hemoglobin, hemoglobin + apotransferrin or hemoglobin + desferrioxamine were co-injected. Twenty-four hours later, anterior uveitis was quantified by slit-lamp examination and determination of protein concentration and infiltration of white cells into the aqueous humor.


RESULTS
Co-injection of autologous hemoglobin with endotoxin greatly exacerbated the ocular inflammatory response to endotoxin, especially the infiltration of white cells, which was increased 15-fold. Both apotransferrin, which binds Fe at high affinity, and desferrioxamine, which chelates Fe, greatly decreased the cellular response to the co-injection.


CONCLUSIONS
It is likely that hemoglobinic Fe is responsible for the increased infiltration of white cells caused by the co-injection of autologous hemaglobin and endotoxin.
Department of Anatomy, Physiology and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA. chris_mcgahan@snl.cvm.ncsu.edu
M C
MC
McGahan
A M
AM
Grimes
L N
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Fleisher
D000818:Animals; D001059:Apoproteins / Q000633:toxicity; D001082:Aqueous Humor / Q000378:metabolism; D003676:Deferoxamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004926:Escherichia coli; D005136:Eye Proteins / Q000378:metabolism; D006454:Hemoglobins / Q000633:toxicity*; D007962:Leukocytes / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D011817:Rabbits; D011897:Random Allocation; D017262:Siderophores / Q000633:toxicity; D014168:Transferrin / Q000633:toxicity; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D014822:Vitreous Body / Q000378:metabolism
D001059:Apoproteins; D004338:Drug Combinations; D005136:Eye Proteins; D006454:Hemoglobins; D008070:Lipopolysaccharides; D017262:Siderophores; D014168:Transferrin; C028284:apotransferrin; D003676:Deferoxamine