Cocaine modulates cytokine and enhances tumor growth through sigma receptors.
Sigma receptors are intracellular receptors that interact with a variety of psychotropic ligands, including cocaine. Administration of cocaine to mice promoted the in vivo growth of a syngeneic lung cancer cell line and identical effects were observed with PRE 084, a selective sigma(1) receptor agonist. Increased tumor growth was accompanied by an increase in IL-10 and a decrease in IFN-gamma production in splenocytes and at the tumor site. The tumor-promoting effects produced by both cocaine and PRE 084 were abrogated by administration of specific antibodies to IL-10, or by administration of a sigma(1) receptor antagonist. We conclude that sigma(1) receptor ligands, including cocaine, augment tumor growth via a cytokine-dependent, receptor-mediated mechanism that involves regulation of T helper 1/T helper 2 cytokine balance.
Gardner
Brian
B
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA 90095, USA. bgardner@mednet.ucla.edu
Zhu
Li X
LX
Roth
Michael D
MD
Tashkin
Donald P
DP
Dubinett
Steven M
SM
Sharma
Sherven
S
D002282:Adenocarcinoma, Bronchiolo-Alveolar; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004347:Drug Interactions; D005029:Ethylenediamines / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D019737:Transplants
D000779:Anesthetics, Local; D000906:Antibodies; D016207:Cytokines; D005029:Ethylenediamines; D009025:Morpholines; D017480:Receptors, sigma; D016753:Interleukin-10; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D007371:Interferon-gamma; D003042:Cocaine