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B and Stimulation of Inhibitor B by Troglitazone: Evidence for an Anti-inflammatory Effect and a Potential Antiatherosclerotic Effect in the Obese
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, New York 14209
Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Ph.D., Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, New York. E-mail: pdandona{at}kaleidahealth.org
To elucidate whether troglitazone exerts an
antiinflammatory effect in humans, in vivo, we
investigated the suppression of nuclear factor 
B (NFB) in
mononuclear cells (MNC) by this drug. We measured intranuclear NFB,
total cellular NFB, inhibitor B (IB)
, reactive oxygen
species (ROS) generation, and p47phox subunit (a key
component protein of nicotinamide adenine dinucleotide phosphate
oxidase) in MNC. Plasma tumor necrosis factor (TNF)-, soluble
intercellular adhesion molecule-1 (sICAM-1), monocyte
chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor
type 1 (PAI-1), C-reactive protein (CRP), and interleukin (IL)-10
(antiinflammatory cytokine) concentrations were also measured as
mediators of inflammatory activity that are regulated by the
proinflammatory transcription factor NFB. Seven nondiabetic obese
patients were given 400 mg troglitazone daily for 4 weeks.
Blood samples were collected before and at weekly intervals thereafter.
MNC were separated; and the levels of intranuclear NFB, total
cellular NFB, IB, and p47 phox subunit and ROS
generation were determined. Plasma was used to measure insulin glucose,
TNF, sICAM, MCP-1, PAI-1, CRP, and IL-10. Plasma insulin
concentrations fell significantly at week 1, from 31.2 ± 29.1 to
14.2 ± 11.4 mU/L (P < 0.01) and remained low
throughout 4 weeks. Plasma glucose concentrations did not alter
significantly. There was a fall in intranuclear NFB, total cellular
NFB, and p47 phox subunit, with an increase in
cellular IB at week 2, which persisted until week 4. There was a
parallel fall in ROS generation by MNC at week 1; this progressed and
persisted until week 4 (P < 0.001). Plasma
TNF-, sICAM-1, MCP-1, and PAI-1 concentrations fell
significantly at week 4. Plasma IL-10 concentration increased
significantly, whereas plasma CRP concentrations decreased. We conclude
that troglitazone has an antiinflammatory action that may
contribute to its putative antiatherosclerotic effects.
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