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Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection.

Kewcharoenwong C, Rinchai D, Utispan K, Suwannasaen D, Bancroft GJ, Ato M, Lertmemongkolchai G - Sci Rep (2013)

Bottom Line: Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei.Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide.These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

View Article: PubMed Central - PubMed

Affiliation: The Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.

ABSTRACT
Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

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Decreased IL-1β and IL-8 production is associated with glibenclamide treatment.IL-1β and IL-8 levels in supernatants were assessed at 16 h after purified PMNs from five subject groups as mentioned infected with B. pseudomallei at an MOI of 0.3:1. Data are expressed as means ± s.d. Asterisks indicate significant differences between not-treated and healthy subjects, and between other DM and not-treated subjects by One Way ANOVA. **P < 0.01, and *P < 0.05. No asterisk or ns, non significant.
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f5: Decreased IL-1β and IL-8 production is associated with glibenclamide treatment.IL-1β and IL-8 levels in supernatants were assessed at 16 h after purified PMNs from five subject groups as mentioned infected with B. pseudomallei at an MOI of 0.3:1. Data are expressed as means ± s.d. Asterisks indicate significant differences between not-treated and healthy subjects, and between other DM and not-treated subjects by One Way ANOVA. **P < 0.01, and *P < 0.05. No asterisk or ns, non significant.

Mentions: To assess whether specific drug treatment regimes for diabetic subjects influence cytokine production by their PMNs, we compared the cytokine production of PMNs isolated from diabetic subjects (see Table 2 for details of subjects). These subjects had similar levels of glycemic control whichever anti-diabetic drug treatment was used (Table 2). As shown in Figure 5B, significantly lower levels (P < 0.05) of IL-1β and IL-8 were produced by PMNs from diabetic subjects who were being treated with glibenclamide compared to PMNs from patients yet to receive treatment (NDM group). In contrast, levels of TNF-α were not significantly different between the various subject groups (data not shown), which indicated that glibenclamide specifically affects IL-1β and IL-8 production by PMNs in response to B. pseudomallei infection.


Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection.

Kewcharoenwong C, Rinchai D, Utispan K, Suwannasaen D, Bancroft GJ, Ato M, Lertmemongkolchai G - Sci Rep (2013)

Decreased IL-1β and IL-8 production is associated with glibenclamide treatment.IL-1β and IL-8 levels in supernatants were assessed at 16 h after purified PMNs from five subject groups as mentioned infected with B. pseudomallei at an MOI of 0.3:1. Data are expressed as means ± s.d. Asterisks indicate significant differences between not-treated and healthy subjects, and between other DM and not-treated subjects by One Way ANOVA. **P < 0.01, and *P < 0.05. No asterisk or ns, non significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842541&req=5

f5: Decreased IL-1β and IL-8 production is associated with glibenclamide treatment.IL-1β and IL-8 levels in supernatants were assessed at 16 h after purified PMNs from five subject groups as mentioned infected with B. pseudomallei at an MOI of 0.3:1. Data are expressed as means ± s.d. Asterisks indicate significant differences between not-treated and healthy subjects, and between other DM and not-treated subjects by One Way ANOVA. **P < 0.01, and *P < 0.05. No asterisk or ns, non significant.
Mentions: To assess whether specific drug treatment regimes for diabetic subjects influence cytokine production by their PMNs, we compared the cytokine production of PMNs isolated from diabetic subjects (see Table 2 for details of subjects). These subjects had similar levels of glycemic control whichever anti-diabetic drug treatment was used (Table 2). As shown in Figure 5B, significantly lower levels (P < 0.05) of IL-1β and IL-8 were produced by PMNs from diabetic subjects who were being treated with glibenclamide compared to PMNs from patients yet to receive treatment (NDM group). In contrast, levels of TNF-α were not significantly different between the various subject groups (data not shown), which indicated that glibenclamide specifically affects IL-1β and IL-8 production by PMNs in response to B. pseudomallei infection.

Bottom Line: Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei.Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide.These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

View Article: PubMed Central - PubMed

Affiliation: The Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.

ABSTRACT
Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

Show MeSH
Related in: MedlinePlus