Troglitazone Exhibits Immunomodulatory Activity on the Cytokine Production of Activated Human Lymphocytes

Abstract

Troglitazone (TGL), a thiazolidinedione compound that improves the response of peripheral target tissue to insulin, also has anti-inflammatory properties, a potential means of protection from Type 1 (insulin dependent) diabetes. In order to test the ability of TGL to affect cytokine production, peripheral blood mononuclear cells from healthy donors were exposed to TGL in the presence or absence of a polyclonal activator (PHA) and the production of cytokines assayed. TGL enhanced PHA response, promoted secretion of the cytokines granulocyte and macrophage colony-stimulating factor and leukaemia inhibitory factor and inhibited tumour necrosis factor-alpha secretion, consistent with causing Th-2 differentiation in T-cells. These results suggest that TGL is capable of modulating cytokine production and could therefore influence Th1/Th2 differentiation.

Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing

“…Troglitazone has been shown to inhibit the hepatitis-B virus 66 and has immunomodulatory effects on cytokine production. 157 It has also been shown to significantly reduce IL-6 levels. 158 …”

Thiazolidinediones May Not Reduce Diabetes Incidence in Type 1 Diabetes

“…Giorgini et al reported that troglitazone reduced proinflammatory cytokines, such as TNF-a and IFN-g in vitro. 4 Augstein et al showed that troglitazone reduced IFN-g expression in splenic T cells in NOD mice. 2 Therefore, it has been hypothesized that thiazolidinediones prevent autoimmune diabetes by suppressing the Th1 skewing of the Th1/Th2 balance seen at the onset of diabetes in NOD mice.…”

Thiazolidinediones for the prevention of diabetes in the non‐obese diabetic (NOD) mouse: implications for human type 1 diabetes

“…There is evidence that TZDs increase insulin synthesis and the insulin content of islet cells in addition to improving the secretory response of islets [19]. In addition to its hypoglycaemic effect, TGL has been shown to possess in vitro antiinflammatory properties as shown by the reduction of cytokines such as TNF-a and IFN-c [20]. TZD activators have been shown to exert anti-inflammatory activities in various cell types by inhibiting the expression of proinflammatory genes such as cytokines, metalloproteases and acute-phase proteins [21].…”