Opioids are drugs that affect sensations such as pain and emotions. They bind to opioid receptors on the surface of cells. The receptors were thought to be in the central nervous system (CNS) only, but is it known now that opioid receptors are found in other parts of the body. The finding has prompted interest in how they may affect the immune system and impact inflammatory conditions in the gut.
Researchers from the University of Tsukuba and Tokyo University of Science are studying the effects of opioids on the immune system. They tested the effects of KNT-127—an artificially synthesized opioid that activates immune responses in live animals and cell cultures. The results point to a promising future for opioids when it comes to treatment of inflammatory bowel disease and other gut ailments.
When mice with IBD were treated with KNT-127, they showed a reduction in a form of colon inflammation called colitis. The favorable effects were indicated by less weight loss and colon atrophy, as well as better disease activity scores. The results were confirmed by other studies.
Study authors say these results are promising. “Before proceeding with additional experiments, we had to rule out the role of CNS opioid receptors in the anti-inflammatory effects of KNT-127,” says co-author Chiharu Nishiyama, a professor at the university, in a statement.
To address this, the researchers performed similar experiments with YNT-2715, which does not cross the blood-brain barrier. The results were similar to those observed with KNT-127. That finding confirmed that the anti-inflammatory effects were mediated via the CNS.
The group found that when the disease was progressing, the opioid reduced the serum levels of a pro-inflammatory factor and the number of macrophages in the mesenteric lymph nodes (MLNs). They also observed an increase in the number of regulatory T cells (Tregs) in MLNs.
The direct effects of KNT-127 on immune cells were consistent with those from animal experiments, with increased secretion of the pro-inflammatory signals as well as enhanced development of Tregs in response to KNT-127 treatment.
“Our findings show that KNT-127 and other activators of opioid receptors could be promising therapeutic options for such diseases,” comments Prof. Nagase, the chief drug developer behind the synthetic opioid.
Nishiyama says that their study represents an important milestone in understanding of the interrelationship between brain and gut function. “Our results on the immune-related effects of opioids, which commonly act on the brain, are steps toward unraveling the biological mechanisms that govern the reciprocative relationship of gut health and the immune system with the CNS,” she adds.
The paper is published in the journal Frontiers in Immunology.