The Development of the Acute Inflammatory Response to Experimental Cutaneous Mucormycosis in Normal and Diabetic Rabbits

Abstract

Previous experiments have shown that the behavior of experimental mucormycotic infection shows striking differences in the normal as compared with the metabolically abnormal host. In rabbits with acute alloxan diabetes and acidosis the inoculation of the fungus produced an acute spreading and fatal infection while the fungus lesions in the metabolically normal host remained confined to the site of inoculation and healed spontaneously (I). These observations referred primarily to fully developed acute lesions. Therefore, the present experiments were designed to compare the development of the inflammatory response to mucormycosis in normal and metabolically abnormal rabbits at various time intervals during the first 24 hours after inoculation. MethodsWhite male rabbits ranging from 1800 to 2300 gin. in weight were used. In 38 animals acute alloxan diabetes with acidosis was produced and the presence of hyperglycemia, glycosuria, and ketonuria were determined as previously described (1). The presence of fully developed acute diabetes was established by blood sugar levels above 400 rag. per cent and 4 plus ketonuria. Forty-one rabbits received no alloxan and served as controls. All 79 animals were inoculated intradermally, without anesthesia, in four sites on the shaved back with 0.3 ml. of a standardized spore suspension of Rhizopus oryzae to which 1 per cent of sterilized India ink had been added to facilitate the identification of the inoculum in the tissues (1). 1Both diabetic and control rabbits were sacrificed at 5, 10, 20, 30, 45, 60 minutes and at 2, 4, 6, 12, and 24 hours after inoculation by intravenous injection of air preceded by 1 cc. of undiluted nembutal administered rapidly. The skin lesions were excised, fixed in Helly's fluid, and each lesion was examined in its entire extent, with multiple sections stained with Giemsa. Complete autopsies were performed and histologic preparations of tissues other than

Tissue Mast Cells and Acute Inflammation in Experimental Cutaneous Mucormycosis of Normal, 48/80-Treated, and Diabetic Rats

“…It is clear from many studies that lowered host resistance to infection resulting from altered host metabolism cannot be attributed to a single factor acting upon one particular mechanism but probably represents the summation of multiple factors interfering with many aspects of the body defenses (6,9,10).…”

“…All animals were inoculated subcutaneously under light ether anesthesia in two sites of the shaved back with 0.2 ml. of a standardized spore suspension of Rhizopus oryzae to which 1 per cent of sterilized India ink had been added to facilitate the identification of the inoculum in the tissues 1 (6). The inoculum was placed into the layer of subcutaneous tissue immediately beneath the corium.…”

“…Three rats each were sacrificed with ether anesthesia at 10, 20, and 30 minutes and at 1, 2, 4, 6, 12, 24, and 48 hours after inoculation. Terminal blood sugar levels were done on blood obtained by cardiac puncture and repeated determinations of urine sugar and acetone were performed on one or more animals for each time interval (6).…”

“…body weight of aUoxan dissolved in normal sterile saline (0.9 per cent NaCI). Hyperglycemia, glycosuria, and acetonuria were determined as previously described (6). All animals were inoculated when acetonuria was 3 plus or greater.…”

“…In the third experiment the influence of a severe, general alteration of host metabolism on the susceptibility to this infection in general and on the tissue mast cells in particular was studied and for this purpose acute alloxan diabetes with acidosis was produced. The same infection was employed in all animals and consisted of the subcutaneous injection of the fungus Rhizopus ory~ae since previous studies had shown that in the normal host mucormycotic infection is self-limiting and remains confined to the site of inoculation while in animals with acute alloxan diabetes and acidosis the infection progresses rapidly and spreads widely (6,7). The results of the experiments were evaluated by histologic examination of the mucormycotic skin lesions.…”