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The role of opioids in protective immune response of carp

Final Activity Report Summary - OPINF (The role of opioids in protective immune response of carp)

Clinical observations show that opiates may affect immunity, and complication in infectious diseases due to opioid abuse are clearly recognised. Although the first data on opioid-induced changes of the immune system were described over a century ago, insight into the mechanisms of interaction between the neuroendocrine and immune systems system is still fragmentary and results are sometimes ambiguous.

The inflammatory reaction is responsible for the rapid recognition of pathogens to prevent pathogen dispersal. Cells of immune system, leukocytes migrate to the focus of infection/inflammation, they phagocytose pathogens and/or produce microbicidal molecules and cytokines. However inflammation-related cells and molecules are double-edged swords as they may be detrimental to the host. Therefore, after pathogen clearance, the inflammatory response must be quickly terminated and processes of tissue remodeling and recovery should be initiated. The kinetics and magnitude of immune responses is strictly regulated by anti-inflammatory cytokines and neuroendocrine mediators (e.g. stress hormones and opioids). Communication between the neuroendocrine and immune systems is possible because they share receptors and mediators. Leukocytes express receptors for neurotransmitters and hormones, while nervous and endocrine organs can respond to cytokines.

In the present project we studied the communication between these systems in carp. Detailed recognition of immune-neuroendocrine interactions of fish broaden our insights into the origin of this cooperation and sheds light on their key biological functions and holds new solutions for treatment or prevention of inflammatory diseases in higher vertebrates, including humans. Moreover, it allows developing and improving strategies in fish health control, which is of pivotal importance considering the increasing importance of aquaculture for the European Community.

We sequenced carp opioid receptors and determined their expression and regulation during both stress and inflammatory responses. We found that carp leukocytes express opioid receptors, and that opioids can modulate the immune response of fish. For example morphine reduces the numbers of inflammatory leukocytes and the level of pro-inflammatory molecules (reactive oxygen species and cytokines) and it decreased the migratory properties of leukocytes. Thus, opioids may have a significant impact on the outcome and duration of an infection. Our work contributes to understanding the regulation of the neuroendocrine and immune responses in fish and it confirms an evolutionary conserved "old" role for the opioid system in maintaining a dynamic equilibrium while coping with stress and/or infection.