Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected withMycobacterium tuberculosis

Abstract

SummaryDiabetes mellitus is an important predisposing factor for tuberculosis. The aim of this study was to investigate the mechanism underlying this association using a murine model. Mice with streptozotocin-induced diabetes mellitus were prone to Mycobacterium tuberculosis infection, as indicated by increased numbers of live bacteria in lung, liver and spleen. In diabetic mice, the levels of IL-12 and IFN-g g g g in the lung, liver and spleen were lower than those in control animals on day 14 postinfection, while the opposite was true for IL-4 levels in the lung and liver. The expression pattern of inducible nitric oxide synthase (iNOS), in the two mice types was as for IL-12 and IFN-g g g g . In addition, peritoneal exudate cells obtained from diabetic mice produced lower amounts of IL-12 and NO than those from control mice, when stimulated in vitro with M. bovis BCG. Spleen cells from diabetic mice infected with M. tuberculosis produced a significantly lower amount of IFN-g g g g upon restimulation with purified protein derivatives (PPD) than those from infected nondiabetic mice. Interestingly, addition of high glucose levels (33 mM) to the cultures of PPD-restimulated spleen cells reduced the synthesis of IFN-g g g g only in diabetic mice, and not in nondiabetic mice. Finally, control of blood glucose levels by insulin therapy resulted in improvement of the impaired host protection and Th1-related cytokine synthesis. Our results suggest that the reduced production of Th1-related cytokines and NO account for the hampered host defense against M. tuberculosis infection under diabetic conditions.

Effects of garlic extract treatment in normal and streptozotocin diabetic rats infected with Candida albicans

“…This situation provides an opportunity for the yeast to grow and produce infectious foci in liver. Yamashiro et al (36) reported that in diabetic mice, the levels of IL-12 and IFN-gamma in liver were lower than those in control animals on day 14 post-infection, while the opposite was true for IL-4 levels. Treatment of normal and diabetic rats with garlic extract after Candida inoculation caused a considerable inhibitory effect on the growth of the organism in both liver and kidneys.…”

Immunological Diagnosis of Active and Latent TB

“…Similarly, metabolic diseases such as diabetes mellitus are known to affect chemotaxis, phagocytosis, activation, and antigen presentation by phagocytes in response to MTB, and this defect does not improve with insulin (Moutschen et al, 1992). Importantly, IFN- production was found to be impared in hyperglycemia (Yamashiro et al, 2005), but another study showed that both IGRA results were not affected in diabetes mellitus patients (Walsh et al, 2011). Intermediate results have been found to be also associated with lower serum albumin and double immunomodulatory therapy (Papay et al,2011).…”

Effect of Glycemic Control on Radiographic Presntation of Pulmonary Tuberculosis in Type 2 Diabetes Mellitus

“…In one study they reported Poor glycemic control significantly influences radiographic manifestations of pulmonary TB in patients with DM; isolated lower lung field involvement and large cavities are more common in uncontrolled diabetics than in optimal control patients [24] . The increased frequency of pulmonary cavitary lesions in diabetic patients with poor glycemic control is probably related to reduced expression of Th1-related cytokines [25] . It is possible that proper glycemic control will not only reduce the risk of tuberculosis among diabetes patients but also attenuates the risk of cavitary lesions of pulmonary TB in diabetic patients.…”