Suppression of humoral and cellular immunity in normal mice by diazepam

Descotes, Jacques; Tédone, R.; Evreux, J C

doi:10.1016/0165-2478(82)90089-x

Cited by 39 publications

(15 citation statements)

References 7 publications

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“…13,14 We speculate, in view of the central role of DCs in the induction of immune response, that the suppressive effects of benzodiazepine on cell-mediated immunity is probably mediated by the effect of benzodiazepine on DCs.…”

Section: Discussionmentioning

confidence: 99%

“…CHS can be also induced by a single subcutaneous injection (day 0) of 5 ϫ 10 5 DCs that have been pulsed with DNBS, followed, on day 5, by epicutaneous challenge with DNFB. 13,14 We used this CHS model with adoptive transfer of DCs to assess the in vivo effect of midazolam on DC-induced Th1-type immune response in the whole animal. Immunization with midazolamtreated DCs elicited less CHS response than immunization with vehicle-treated DCs ( fig.…”

Section: Midazolam-treated Dcs Failed To Elicit Chs That Would Normalmentioning

confidence: 99%

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Midazolam Suppresses Maturation of Murine Dendritic Cells and Priming of Lipopolysaccharide-induced T Helper 1-type Immune Response

et al. 2011

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Background: Dendritic cells (DCs), as antigen-presenting cells, play a key role in the induction and regulation of adaptive immune response. Midazolam is reported to have immunomodulatory properties that affect immune cells. However, the effect of midazolam on DCs has not been characterized. We examined the immunomodulatory properties of midazolam on DC-mediated immune response. Methods: After allowing murine bone marrow-derived DCs induced by granulocyte macrophage colony stimulating factor to mature, we analyzed their expression of costimulatory molecules (CD80 and CD86), major histocompatibility complex class II molecules, and the secretion of interleukin-12 p40. In vitro, we evaluated the effect of midazolam on maturing DCs in mixed cell cultures containing DCs and T cells. In vivo, we investigated the contact-hypersensitivity response. Results: Midazolam suppressed the expression of CD80, CD86, and major histocompatibility complex class II molecules from murine DCs. Treated with midazolam, DCs also secreted less interleukin-12 p40. In mixed cell cultures with CD3-positive T cells, midazolam-treated DCs showed less propensity to stimulate the proliferation of CD3-positive T

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Section: Discussionmentioning

confidence: 99%

Section: Midazolam-treated Dcs Failed To Elicit Chs That Would Normalmentioning

confidence: 99%

Midazolam Suppresses Maturation of Murine Dendritic Cells and Priming of Lipopolysaccharide-induced T Helper 1-type Immune Response

et al. 2011

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“…Also, the absence of changes in corticosterone levels in male fetuses and offspring of diazepam-exposed dams [7] indicated no essential pri mary role of a neuroendocrine link. There fore, we analyzed also the potential role of the peripheral-type BDZ receptor in this Potential hazards to the immune system may result from exposure to a number of drugs and environmental chemicals such as opioids [1], alcohol [2], heavy metals [3], and benzodiazepines (BDZ) [4], Recently we re ported on a long-lasting immunosuppression as a consequence of prenatal BDZ treatment [5], Allogeneic and mitogen-induced T lym phocyte proliferation was reduced in off spring of mothers treated with a low dose of diazepam or clonazepam from gestational day (GD) [14][15][16][17][18][19][20]. While diazepam is a BDZ phosphate buffer for 2 h at 4 °C.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Benzodiazepine Immunosuppression: Possible Involvement of Peripheral Benzodiazepine Site

Schlumpf¹,

Parmar²,

Ramseier³

et al. 1990

Dev Pharmacol Ther

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Treatment of pregnant Long Evans rats with a low dose of diazepam (1.25 mg/kg from gestational day 14-20) produced offspring suffering from suppression of cellular immune responses. Analogous effects were produced by clonazepam, a benzodiazepine (BDZ) with high affinity for the central-type, and Ro 5-4864, a BDZ with selective affinity for the peripheral-type BDZ receptor. Peripheral-type BDZ receptors are found to develop early in fetal life in peripheral organs including primary (thymus) and secondary (spleen) lymphoid organs, in the central nervous system and on immune cells (lymphocytes). In prenatally diazepam-exposed offspring the affinity constant is significantly changed. BDZ and PK 11195 also inhibit mitogen and alloantigen-induced T and B cell proliferation in vitro in adult murine lymphocytes. Diazepam, Ro 5-4864 and PK 11195 were found to be the most active compounds.

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“…A wide range of drugs and environmental chemicals have been found to influence the immune system in adult animals [1,2], but very little is known of such drug effects during prenatal development. The administration of the benzodiazepine (BDZ), diazepam, to pregnant rats during the last week of gestation resulted in long-lasting behavioural and neurochemical changes in the offspring [3].…”

Section: Introductionmentioning

confidence: 99%

The effect of prenatal diazepam exposure on TNF-α production by rat splenocytes

et al. 1993

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Prenatal exposure to diazepam and other benzodiazepines (BDZ) has been found to result in a marked reduction of T-lymphocyte proliferation during postnatal development of rats. In search for pathogenic changes underlying this effect, we investigated the mitogen lipopolysaccharide (LPS) and concanavalin A (ConA) stimulated release of tumour necrosis factor (TNF)-alpha by mixed splenocytes of male offspring from Long Evans rats treated with 1.25 mg/kg per day diazepam from gestational day 14 to 20. In response to LPS, TNF-alpha release was found to be significantly lower in mixed splenocytes of two- and four-week-old treated than in control offspring. However, at eight weeks of age, prenatally diazepam-treated animals showed a significantly higher LPS-induced TNF-alpha release than control rats. Since monocytes/macrophages represent a major source of TNF-alpha, additional experiments were performed on purified spleen macrophages and lymphocytes stimulated with LPS. TNF-alpha release was only detectable in supernatants of adherent spleen macrophages and not in supernatants of lymphocytes. Thus, our data indicate that a disturbance in TNF-alpha release from macrophages is involved in the deficient immune response of prenatally diazepam-exposed rats.

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Suppression of humoral and cellular immunity in normal mice by diazepam

Cited by 39 publications

References 7 publications

Midazolam Suppresses Maturation of Murine Dendritic Cells and Priming of Lipopolysaccharide-induced T Helper 1-type Immune Response

Midazolam Suppresses Maturation of Murine Dendritic Cells and Priming of Lipopolysaccharide-induced T Helper 1-type Immune Response

Prenatal Benzodiazepine Immunosuppression: Possible Involvement of Peripheral Benzodiazepine Site

The effect of prenatal diazepam exposure on TNF-α production by rat splenocytes

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