The Effect of Methadone on the Immune Status of B6C3F1 Mice
| Autor: | Louis S. Harris, Brown Rd, Albert E. Munson, J. A. Mccay, D. L. Musgrove, Kimber L. White, Leon F. Butterworth, Bruce A. Fuchs, D G Levier |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
Erythrocytes B-Lymphocyte Subsets Mice Inbred Strains Spleen Toxicology Pneumococcal Infections Mice Subcutaneous injection chemistry.chemical_compound T-Lymphocyte Subsets Corticosterone Internal medicine medicine Animals Listeriosis Mononuclear Phagocyte System business.industry Body Weight Immunity Endocrinology medicine.anatomical_structure Immunoglobulin M chemistry Mice Inbred DBA Toxicity Morphine Female Opiate business Methadone Hypothalamic–pituitary–adrenal axis Half-Life medicine.drug |
| Zdroj: | Fundamental and Applied Toxicology. 24:275-284 |
| ISSN: | 0272-0590 |
| DOI: | 10.1006/faat.1995.1030 |
| Popis: | The Effect of Methadone on the Immune Status of B6C3F1 Mice. LeVier, D. G., Brown, R. D., Musgrove, D. L., Butterworth, L. F., McCay, J. A., White, K. L., Jr., Fuchs, B. A., Harris, L. S., and Munson, A. E. (1995). Fundam. Appl. Toxicol. 24, 275-284. Previously, morphine has been shown to elevate corticosterone via the hypothalamic-pituitary-adrenal axis and to suppress the immune system. The present investigation sought to determine if the μ-opiate receptor agonist methadone incurred a similar immune suppression in B6C3F1 mice. Serum methadone and corticosterone levels peaked 1 hr following a single subcutaneous injection of 20 mg/kg methadone HCl. Indeed, the rise in corticosterone levels paralleled that of methadone. After a single injection with 20 mg/kg methadone a pharmacokinetic analysis revealed a serum half-life of ≈2 hr. Following five injections of methadone over a 24-hr period (every 6 hr), methadone levels were elevated as would be expected; however, corticosterone levels did not become elevated. This suggests that the ability of methadone to elevate corticosterone becomes uncoupled following repeated dosing, indicative of either a tolerance or an increased catabolic mechanism. Moreover, dosing every 6 hr for 5 days induced an increase in the catabolism of methadone itself. Therefore, all assays were begun 1 hr after subcutaneous administration of methadone HCl, a time at which both methadone and corticosterone serum levels were elevated. The primary IgM antibody response to sheep red blood cells (sRBC) was suppressed when splenocytes were immunized in vitro . In contrast, animals immunized with sRBC and assayed for the primary IgM antibody response 4 days later were not suppressed. The activity of the resident macrophages of the liver and spleen as measured by the uptake of 51 Cr-sRBC was suppressed in a dose-dependent manner. Previously, it has been demonstrated that morphine suppresses hepatic and splenic phagocytic activity through an opiate receptor-mediated pathway that involves the release of corticosterone. It would appear that methadone plays a similar role in the suppression of hepatic and splenic phagocytosis. |
| Databáze: | OpenAIRE |
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