The parasitic worm Ascaris suum contains the opiate alkaloid morphine as determined by HPLC coupled to electrochemical detection and by gas chromatography/mass spectrometry. The level of this material is 1168 ± 278 ng/g worm wet weight. Furthermore, Ascaris maintained for 5 days contained a significant amount of morphine, as did their medium, demonstrating their ability to synthesize the opiate alkaloid. To determine whether the morphine was active, we exposed human monocytes to the material, and they immediately released nitric oxide in a naloxone-reversible manner. The anatomic distribution of morphine immunoreactivity reveals that the material is in the subcuticle layers and in the animals’ nerve chords. Furthermore, as determined by RT-PCR, Ascaris does not express the transcript of the neuronal μ receptor. Failure to demonstrate the expression of this opioid receptor, as well as the morphine-like tissue localization in Ascaris, suggests that the endogenous morphine is intended for secretion into the microenvironment.
Successful parasitism, in which the host survives for extended periods, can be characterized as an equilibrium between the parasite and the host, more specifically between the host’s immune system and the parasite’s ability to create a permissive microenvironment in situ. One mechanism that a parasite may use to modify the host immune response is to down-regulate the host’s response (1, 2, 3). Capron and colleagues (4, 5, 6, 7) suggested that parasites may communicate with their hosts via common signaling molecules that diminish host immune surveillance. In this regard, morphine is generally acknowledged as an immune down-regulating agent (8). This finding is enhanced by the fact that morphine is present in several mammalian tissues, including brain and adrenal gland (9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20), supporting its role as a neural or inflammatory mediator.
Recently, we have demonstrated that free-living and parasitic invertebrates produce several major opioid peptide precursors, i.e., prodynorphin, proopiomelanocortin, and proenkephalin (21). These mammalian-like opioid peptides exhibit high sequence identity to their mammalian counterparts. For example, Mytilus adrenocorticotropin has greater than 90% sequence identity with its mammalian counterpart (21). We have also identified a tentative morphine-like molecule in Schistosoma mansoni by way of radioimmunoassay (22).
Given this and the fact that the pig intestinal parasite Ascaris suum can live in its host for extended periods of time, we surmised that it might be using morphine to escape detection by the host’s immune system. In this study, we report for the first time that A. suum synthesizes morphine, thereby strengthening the common-signal molecule hypothesis, i.e., using either similar or identical host signaling to escape host immunosurveillance.