Studies on the effect of experimental nonketotic diabetes mellitus on antibacterial defense. I. Demonstration of a defect in phagocytosis.
Chronically diabetic nonketotic rats were shown to be more susceptible to experimental Type 25 pneumococcal pneumonia than nondiabetic rats. The cumulative mortality in the diabetic group was significantly higher at infecting doses of 10(3), 10(4), 10(5), and 10(6) organisms, and the LD(50) was less than one twentieth of that for the nondiabetic group. More than ten times as many viable pneumococci were found in the pneumonic lesions of the diabetic animals at 24 and 36 hr as were present in the lesions of the nondiabetic controls, and serial histologic studies revealed that phagocytosis was strikingly depressed in the alveolar exudates of the diabetic animals. The diabetic state was also found to cause a similar depression of in vivo phagocytosis in preformed peritoneal exudates. The results of in vitro experiments indicated that the principal defect in the diabetic animals resided in their serum rather than in their polymorphonuclear leukocytes. The depressive factor in the serum was identified as the abnormally high concentration of glucose. Since equivalent molar concentrations of unmetabolized sugars added to normal serum caused a similar depression of phagocytosis, it was tentatively concluded that the action of the glucose on the leukocytes was primarily osmotic. The sensitivity of the granulocytes to the glucose effect, however, depended upon the conditions of the phagocytic test. Only when the pneumococci were encapsulated and the leukocytes derived from inflammatory exudates were crowded together, as in vivo, was the depressive action of the glucose clearly demonstrable.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007958:Leukocyte Count; D010587:Phagocytosis; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D051381:Rats; D013296:Streptococcus pneumoniae; D013395:Sucrose / Q000494:pharmacology
D013395:Sucrose; D005947:Glucose