Chronic exposure of human macrophages in vitro to morphine and methadone induces a putative tolerant/dependent state.
We have shown previously that whereas acute exposure of cultured murine peritoneal macrophages inhibits phagocytosis, chronic exposure results in a putative tolerant/dependent state. We now report similar observations using human cultured monocyte-derived macrophages (hMDM) from a control population and from methadone patients. With hMDM, acute exposure to morphine and methadone inhibited phagocytosis in a dose-dependent manner. In contrast, chronic exposure resulted in eventual normalization of phagocytosis, indicating that a putative tolerant state to the opiates had developed. When opiates were withdrawn from chronically-exposed, tolerized hMDM, phagocytosis was once again depressed. The duration of withdrawal-induced depression lasted several hours, which is much longer than evidenced previously with murine macrophages. These data identify well with various in vivo studies on immune effects of opiate withdrawal; and, in so-doing, supplement ongoing speculation that opiate withdrawal is likely to have serious impact on host defenses of street heroin addicts.
Delgado-Vélez
Manuel
M
Biology Department, University of Puerto Rico, Río Piedras Campus, POB 23360, San Juan, Puerto Rico 00931-3360.
Lugo-Chinchilla
Ana
A
Lizardo
Luis
L
Morales
Irmarie
I
Robles
Yarelis
Y
Bruno
Nimaris
N
Rodríguez
José W
JW
Ríos-Olivares
Eddy
E
Correa
Miguel
M
Renaud
Fernando L
FL
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D008691:Methadone