Vanderbilt University Medical Center study sheds light on side effects of COX-2 drugs

November 12, 2015

It's been about a decade since the promise of COX-2 inhibitors -- drugs that relieve arthritis pain and inflammation without the gastrointestinal side effects of other painkillers -- was tempered by the realization that they could cause heart problems in some patients.

Now a team of Vanderbilt University Medical Center scientists led by Ming-Zhi Zhang M.D., M.Sc., and Raymond C. Harris, M.D., are closer to understanding why. They have found that production of prostaglandins by macrophages may play a role, especially in the kidney and the skin.

Their findings, published in the Journal of Clinical Investigation, could lead to development of a new, better-targeted class of drugs that relieve pain without causing vascular effects.

Prostaglandins are molecules produced by the cyclooxygenase enzymes -- COX-1 and COX-2 -- that play a role in inflammation, among other wide-ranging effects. Macrophages, a kind of white blood cells, also are involved in inflammation.

However, prostaglandin production by macrophages also seems to have a protective effect on heart function, by modulating hyper tension and edema -- fluid retention -- in response to a high-salt diet.

In a study in mice, the Vanderbilt researchers found that when the COX-2 enzyme in macrophages was blocked, and thus prevented from making prostaglandins, hypertension and edema got worse.

As researchers understand this pathway better, the hope is that they will be able to develop new drugs to relieve pain and inflammation without affecting the system that regulates blood pressure and fluid retention. That would be closer to fulfilling the promise of the original COX-2 inhibitors.
-end-
Zhang is assistant professor of Medicine and Cancer Biology. Harris is the Ann and Roscoe R. Robinson Professor of Nephrology and director of the Division of Nephrology.

The research was supported in part by National Institutes of Health grants CA122620, DK038226, DK062794, and DK095785.

Vanderbilt University Medical Center

Related Macrophages Articles from Brightsurf:

New technology tracks role of macrophages in cancer spread
A Morgridge imaging study of macrophages -- immune cells that are important to human health, but paradoxically can help some cancers grow and spread -- is offering better ways to understand these cells and target them with immunotherapies.

UCalgary researchers discover how to capture images of cells at work inside our lungs
University of Calgary scientists have discovered how to capture ''live'' images of immune cells inside the lungs.

Researchers characterize important regulators of tissue inflammation, fibrosis and regeneration
Although macrophages (cells involved in the detection and destruction of bacteria and other harmful organisms as well as dead cells) are classified as immune cells functioning in the activation and resolution of tissue inflammation, it is now clear that they are critically involved in a variety of disease processes, such as chronic inflammatory diseases, tumor growth and metastasis and tissue fibrosis.

Assembly within the tumor center
Number of macrophages in tumor tissue enables prognosis of lung tumor progression.

'Cells-soldiers' turned to be more resistant than 'cells-combat medics'
Researchers from Sechenov University (Russia) and University of Pittsburgh (USA) discovered that the resistance of innate immune cells, macrophages, to ferroptosis -- a type of programmed cell death -- depends on the type of their activation.

New molecular mechanism that regulates the sentinel cells of the immune system
CNIC scientists have uncovered a new molecular mechanism that determines the identity and expansion of one of the cell types that work as immune sentinels in the body -- the macrophages of the serous cavities.

CAR macrophages go beyond T cells to fight solid tumors
Penn Medicine research shows genetically engineering macrophages -- an immune cell that eats invaders in the body -- could be the key to unlocking cellular therapies that effectively target solid tumors

Stroke: Macrophages migrate from the blood
Macrophages are part of the innate immune system and essential for brain development and function.

Double trouble: A drug for alcoholism can also treat cancer by targeting macrophages
The deadly nature of cancer stems from its ability to spread and grow inside the host.

Immune response in brain, spinal cord could offer clues to treating neurological diseases
An unexpected research finding is providing information that could lead to new treatments of certain neurological diseases and disorders, including multiple sclerosis and Alzheimer's.

Read More: Macrophages News and Macrophages Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.