Function for the opioid system during inflammation in teleost fish

In mammals the opioid system is involved in modulation of both innate and acquired immune responses, thus altering resistance to a variety of infectious agents. Opioids can affect immune responses either indirectly, when they stimulate release of cortiocosteroids and/or catecholamines and directly via opioid receptors on leukocytes. Interestingly, specific opioid receptor types have been identified on nonmammalian immunocytes. We have studied the effects of different opioid ligands on innate immune responses of common carp. We sequenced and characterised carp mu, delta and kappa opioid receptors. Moreover, expression profiles of these receptors in different lymphoid organs and specific leukocyte cell populations were studied. In in vitro conditions morphine (agonist of mu3 opioid receptor) reduced gene expression of pro-inflammatory cytokines/chemokines, NO production, chemotaxis and apoptosis of head kidney leukocytes, but did not affect respiratory burst. Furthermore, morphine injected locally to the focus of inflammation during peritonitis reduced the influx of inflammatory leukocytes and downregulated expression of pro-inflammatory mediators (e.g. TNF-a, chemokines, iNOS) and chemokine. Also delta (deltorphine II) and kappa (U50, 488H) opioid receptor agonists modified in vitro leukocyte activity. Our experiments led to the hypothesis that the phylogenetically conserved anti-inflammatory function of opioids includes release of endogenous opioid peptides. Such opioid-dependent modifications of the inflammatory process will be advantageous to the host, because inflammation-related cells and molecules are double-edged nd their high concentration and/or prolonged action may be detrimental.