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Cocaine down-regulates IL-2-induced peripheral blood lymphocyte IL-8 and IFN-gamma production. 1996

J T Mao, and M Huang, and J Wang, and S Sharma, and D P Tashkin, and S M Dubinett
Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 90073, USA.

Cocaine has multiple immunomodulatory effects, including the ability to influence cytokine release in immunoeffector cells. Little is known, however, regarding the effects of cocaine on cytokine production by human peripheral blood lymphocytes (PBL). The effect of cocaine on PBL cytokine profiles and the molecular mechanisms responsible for the modulation of cytokine mRNA expression were investigated. To evaluate the effects of cocaine on cytokine production, conditioned supernatant from IL-2-stimulated PBL was evaluated by cytokine-specific ELISA (IL-4, IL-5, IL-8, IL-10, IFN-gamma, and TGF-beta) following in vitro cocaine exposure. Cocaine abrogated the IL-2-induced production of IFN-gamma and IL-8 in a dose-responsive manner. Cocaine also decreased PBL IFN-gamma and IL-8 mRNA expression as determined by Northern blot and slot blot analysis. Cocaine did not affect the stability of the IFN-gamma and IL-8 mRNA. Nuclear run-on assays revealed that cocaine down-regulated the rate of IFN-gamma and IL-8 transcription. These findings suggest that the immunomodulatory effects of cocaine may be mediated, in part, by modification of lymphocyte cytokine production.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016209 Interleukin-8 A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. CXCL8 Chemokine,Chemokine CXCL8,Chemotactic Factor, Macrophage-Derived,Chemotactic Factor, Neutrophil, Monocyte-Derived,IL-8,Neutrophil-Activating Peptide, Lymphocyte-Derived,Neutrophil-Activating Peptide, Monocyte-Derived,AMCF-I,Alveolar Macrophage Chemotactic Factor-I,Anionic Neutrophil-Activating Peptide,Chemokines, CXCL8,Chemotactic Factor, Neutrophil,Granulocyte Chemotactic Peptide-Interleukin-8,IL8,Monocyte-Derived Neutrophil Chemotactic Factor,Neutrophil Activation Factor,Alveolar Macrophage Chemotactic Factor I,Anionic Neutrophil Activating Peptide,CXCL8 Chemokines,CXCL8, Chemokine,Chemokine, CXCL8,Chemotactic Factor, Macrophage Derived,Chemotactic Peptide-Interleukin-8, Granulocyte,Granulocyte Chemotactic Peptide Interleukin 8,Interleukin 8,Lymphocyte-Derived Neutrophil-Activating Peptide,Macrophage-Derived Chemotactic Factor,Monocyte-Derived Neutrophil-Activating Peptide,Neutrophil Activating Peptide, Lymphocyte Derived,Neutrophil Activating Peptide, Monocyte Derived,Neutrophil Chemotactic Factor,Neutrophil-Activating Peptide, Anionic,Peptide, Anionic Neutrophil-Activating

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