Dr Chidchamai Kewcharoenwong
Khon Kaen University, Thailand
Glibenclamide alters cytokine production of primary human monocytes from diabetic individuals against Mycobacterium tuberculosis infection
Type 2 diabetes mellitus (T2DM) is an important risk factor for development of tuberculosis (TB). Our previous study showed glibenclamide, an anti-diabetic drug used to control blood glucose levels, reduced interleukin(IL)-8 secretion from primary human monocytes challenged with M. tuberculosis (Mtb). In mice infected with Mtb, IL-1β is essential for host resistance through the enhancement of cyclooxygenase that limits excessive Type I interferon (IFN) production and promotes Mtb containment. We hypothesize that glibenclamide may also interfere with cell-mediated immune responses against Mtb in humans and alter the balance between IL-1β and Type I interferon-mediated immunity. Purified monocytes from non-diabetic and diabetic individuals were infected with Mtb or M.bovis BCG. We demonstrate that monocytes from diabetic individuals who were being treated with glibenclamide showed reduced IL-1β and IL-8 secretion when exposed to Mtb compared with other anti-diabetic drugs or non-diabetic individuals. These responses were also impaired when monocytes from non-diabetic individuals were pre-treated with glibenclamide in vitro. This pre-treatment enhanced monocyte expression of IFNa1 mRNA but did not alter prostaglandin E2 (PGE2) level in response to Mtb infection. Taken together, our data show that glibenclamide might exacerbate susceptibility of diabetic individuals to Mtb infection by reducing IL-1β and IL-8 production by monocytes.
I have taken the first steps towards translating my research findings on the effect of anti-DM drugs on B. pseudomallei infection into policy change. Another major infectious challenge for diabetic patients in Thailand is TB, also a major public health problem across the world. Although there is a strong TB public health community in Thailand but there is little or no clinical/laboratory research on the important interactions between the bacteria and the host immune response. I expect to disseminate the novel knowledge by publishing my study in journals with high impact factors, which will help to amplify my research to public health policy makers not only from Thailand but also, from other lowmedium income countries. I aim for my work to have a major impact on public health policy by developing the treatment recommendations for TB with DM individuals and on vaccine development for melioidosis and TB. I also aim to help Thailand to become a world leader in the management of bacterial infection in DM individuals.