The thymolytic effect of cocaine and monoaminergic drugs in the mouse

Choi, Sunju; Yoon, Kyoung‐Jin; Park, Kwan-Kyun; Ngong, Josephine M.; Soliman, Karam F.A.

doi:10.1016/s0024-3205(98)00008-3

Cited by 4 publications

(7 citation statements)

References 22 publications

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“…Cocaine is a recognized immunosuppressant and has been demonstrated in murine models to have a direct effect on the thymus. [19][20][21] Our results demonstrate that cocaine use is also associated with depressed thymic endocrine function. The association of cocaine use with both lower thymulin activity and a greater decline in thymulin activity over time was independent of viral load and ART.…”

Section: Discussionmentioning

confidence: 53%

“…16 Numerous murine studies have shown a decrease in thymus weight, total number of thymocytes, number of immature thymocytes, and T cell response to mitogens with exposure to cocaine. [17][18][19] The thymic atrophy associated with cocaine appears to be due to a direct inhibition on thymocyte DNA synthesis and increased thymocyte apoptosis. 19,20 Studies with murine AIDS models have shown that cocaine use may further potentiate changes in CD4 þ and CD8 þ cell counts that occur with HIV infection.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19] The thymic atrophy associated with cocaine appears to be due to a direct inhibition on thymocyte DNA synthesis and increased thymocyte apoptosis. 19,20 Studies with murine AIDS models have shown that cocaine use may further potentiate changes in CD4 þ and CD8 þ cell counts that occur with HIV infection. 21 The direct effect of cocaine on immune function, and the potentiation of effects of HIV on immune parameters, and on disease progression independent of antiretroviral therapy (ART) adherence, suggests that cocaine may accelerate HIV disease through an additional mechanism unrelated to antiretroviral adherence.…”

Section: Introductionmentioning

confidence: 99%

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Cocaine Reduces Thymic Endocrine Function: Another Mechanism for Accelerated HIV Disease Progression

Rafie

Campa

Smith

et al. 2011

AIDS Research and Human Retroviruses

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Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4(+) cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherence to antiretroviral medication. Recent findings of an association between cocaine use and decline in CD4(+) cell counts independent of antiretroviral adherence indicate alternative mechanisms for disease progression. We evaluated the relationship between thymulin activity, CD4(+) and CD8(+) cell counts and the CD4(+)/CD8(+) ratio, and the covariate effects of substance use cross-sectionally in 80 HIV(+) active substance users and over 12 months in 40 participants. Thymulin activity was analyzed in plasma using a modification of the sheep rosette bioassay. Thymulin activity was negatively associated with cocaine use (β = -0.908,95% CI: -1.704, -0.112; p = 0.026). Compared to those who do not use cocaine, cocaine users were 37% less likely to have detectable thymulin activity (RR = 0.634, 95% CI: 0.406, 0.989 p = 0.045) and were 75 times more likely to show a decrease in thymulin activity (OR = 74.7, 95% CI: 1.59, 3519.74; p = 0.028) over time. CD4(+) cell count was positively associated with thymulin activity (β = 0.127, 95% CI: 0.048,0.205; p = 0.002), detectable thymulin activity was 2.32 times more likely in those with a CD4 cell count ≥200 cells/μl (RR = 2.324, 95% CI: 1.196, 4.513, p = 0.013), and those with an increase in CD4 cell counts were more likely to show an increase in thymulin activity (OR = 1.02, 95% CI: 1.00, 1.034; p = 0.041) over time. Thymulin activity is predictive of HIV disease progression and is depressed in cocaine users independent of antiretroviral treatment (ART) and HIV viral load. Understanding the mechanisms for accelerated HIV disease progression provides opportunities to find alternative strategies to counteract immunosuppression.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cocaine Reduces Thymic Endocrine Function: Another Mechanism for Accelerated HIV Disease Progression

Rafie

Campa

Smith

et al. 2011

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

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“…[22] When thymus glands were removed from HSD-NDA male Swiss mice fed with cocaine solution (200 mg/L) for 10 days, it was shown that cocaine inhibited [3H] thymidine uptake into DNA in a dose-dependent manner. [23] These results suggest that cocaine affects both thymocyte differentiation and proliferation.…”

Section: Introductionmentioning

confidence: 91%

Evidence of Increased DNA Content of Murine Thymocytes Caused by Cocaine

Hagen

Shen

et al. 2003

Immunopharmacology and Immunotoxicology

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C57BL mice were injected intraperitoneally daily with 10 to 50 mg/kg of cocaine for five days. Four hours after the last injection, the thymuses were removed, and the effects on DNA and protein content of the surviving cells were measured. A dose-dependent increase in DNA content per cell, determined by UV spectrophotometric analysis, and a dose-dependent increase in protein content per cell, as measured using the Bio-Rad reagent, were observed. The increase in DNA content per cell was confirmed by H33258 staining of DNA as well as the diphenylamine assay. These changes were also observed when normal thymocytes were cultured with cocaine. Cell cycle analysis by flow cytometry of cocaine-treated cultures revealed the presence of aneuploid cells with increased DNA content. Fewer cells with aneuploidy were observed in experiments with significant apoptosis. Since both aneuploidy and enhanced apoptosis can be induced by cocaine and the amount of aneuploidy cells varies inversely with the degree of apoptosis, we hypothesize that cocaine causes DNA/chromosome damage, which eventually leads to cell death via the apoptosis pathway.

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“…Furthermore, cocaine also affects the immune system negatively, at least in part by altering the functional status of lymphoid organs including the thymus and spleen. For example, it has been shown both in vivo and in vitro that cocaine negatively regulates the proliferation of splenic T-lymphocytes as well as thymocytes [ 5 , 6 ]. Recently, we showed that the intraperitoneal administration of 50 mg/kg cocaine once a day for a week results in sustained splenic contraction, although we did not examine the possibility that the thymus was also affected by this treatment [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Thymic involution caused by repeated cocaine administration includes apoptotic cell loss followed by ectopic adipogenesis

et al. 2022

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Cocaine abuse has a negative impact on the immune system. To investigate the adverse effects of binge cocaine administration on lymphoid organs such as thymus and spleen, we examined the effects of repeated intravenous (i.v.) administration of cocaine on rats. Sprague Dawley rats (male, 8 weeks old) received 20 mg/kg body weight of cocaine hydrochloride per day for 7 or 14 days. In addition to a significant loss in the weight of the spleen, consistent with our previous intraperitoneal (i.p.) injection model of binge cocaine abuse (50 mg/kg cocaine for 7 days), we also found a significant loss of weight as well as apparent shrinkage of the thymus in the cocaine group. Transcriptome analysis of the thymus revealed increased expressions of genes involved in apoptosis, such as Ifi27 and Traf2, as well as decreased expressions of several genes related to lipid metabolism, such as Cd36, Adipoq, Scd1, and Fabp4, in the thymus of the cocaine group (7 days), suggesting an apoptotic loss of thymic cells as well as alterations in lipid metabolism. Paradoxically, cocaine activates PPARγ, a key transcriptional factor activating lipid metabolism, although ectopic adipogenesis was scarcely observed in the thymus. Further analysis of rats administered 20 mg/kg cocaine for 14 days revealed ectopic adipogenesis, which was accompanied with the activation of PPARγ as well as increased expression of Adipoq and Fabp4, in the thymus. Taken together, these results indicate that repeated cocaine administration induces thymic involution, which is initiated by the loss of thymic cells through apoptosis and subsequent ectopic adipocyte development.

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The thymolytic effect of cocaine and monoaminergic drugs in the mouse

Cited by 4 publications

References 22 publications

Cocaine Reduces Thymic Endocrine Function: Another Mechanism for Accelerated HIV Disease Progression

Cocaine Reduces Thymic Endocrine Function: Another Mechanism for Accelerated HIV Disease Progression

Evidence of Increased DNA Content of Murine Thymocytes Caused by Cocaine

Thymic involution caused by repeated cocaine administration includes apoptotic cell loss followed by ectopic adipogenesis

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