Effect of prolonged exposure to morphine on responsiveness of human and invertebrate immunocytes to stimulatory molecules.
This study deals with a novel role of morphine in the modulation of cellular responsiveness to immunostimulatory substances that, at first glance, appears to be in contrast to the well documented immunoinhibitory short-term effects of opiate alkaloids on cells simultaneously exposed to stimulatory molecules. Vertebrate and invertebrate immunocytes pre-exposed to morphine (10(-6) M) in vitro for at least 24 h prior to the administration of lipopolysaccharide (LPS; 1.0 micrograms/ml) or other immunoactivating substances have revealed a distinct enhancement of their responsiveness to these signals, e.g. monocytes exposed to LPS alone resulted in 21% activation, whereas the morphine pretreated level was at 40% (P < 0.01). Prolonged pretreatment with morphine of naive human monocytes had the same effect on their sensitivity to plasma from patients having undergone cardiopulmonary bypass (CPB) operations followed by a diffuse inflammatory response. These results suggest that endogenous opiates may participate, in more than one way, in re-establishing an organism's readiness to meet a new demand on its immune system. Additional support for the concept of a role of endogenous opiates in immunomodulation was obtained by the results of in vivo tests with experimentally induced stress in Mytilus. Following their stress-induced stimulation, these animals' immunocytes could be shown to become exposed for some time to a measurable rise in endogenous morphine-like material (9 pmol/ml increasing to 59). These immunocytes, like those preincubated with exogenous morphine, displayed a heightened sensitivity to stimulation by LPS (control 21.3 +/- 3.1% activation compared to 47.2 +/- 5.1) when the morphine levels dropped. The mechanism of this enhancement of responsiveness to immunostimulation following the prolonged exposure of immunocytes to morphine, and its relationship with the known short-term immunoinhibitory opiate effects on the immune system, remains to be ascertained.
Multidisciplinary Center for the Study of Aging, Old Westbury Neuroscience Research Institute, State University of New York 11568, USA.
G B
GB
Stefano
M K
MK
Leung
T V
TV
Bilfinger
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B
Scharrer
D000818:Animals; D049872:Bivalvia / Q000276:immunology*; D004744:Enkephalin, Methionine / Q000032:analysis; D006458:Hemolymph / Q000737:chemistry; D006801:Humans; D007114:Immunization; D007313:Insecta / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D009020:Morphine / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004744:Enkephalin, Methionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine