title: Disruption of Th1/Th2 cytokine balance by cocaine is mediated by corticosterone.
abstract: Cocaine has been shown to affect immune function through the release of corticosterone. Acute administration of both cocaine and corticosterone produces an enhancement of the T-dependent antibody response to sheep erythrocytes. The T-independent antibody response to DNP-ficoll is not enhanced under identical conditions, suggesting that the T-cell is involved as a cellular target. We examined T-helper cell cytokine production following in vivo cocaine administration and found an increase in IL-4 and IL-10; while IL-2 and IFN-gamma were unaffected. The rise in Th2 cytokines is consistent with an enhanced T-dependent antibody response, a measure of humoral immunity. Because previous results showed that the enhancement by cocaine is mediated via corticosterone, the direct effects of corticosterone on Th1/Th2 in vitro cytokine production were investigated. Th1 cytokines, IL-2 and IFN-gamma, were dose-dependently suppressed by corticosterone at physiologic concentrations. In contrast Th2 cytokines, IL-4 and IL-10, exhibited a biphasic dose response curve, whereby an enhancement was observed at low doses, followed by suppression at higher doses. In order to determine the consequences of this apparent shift towards a Th2 response on a Th1 response, we looked at the delayed-type hypersensitivity response to sheep erythrocytes. This measure of cell-mediated immunity was not significantly affected by acute cocaine, however, corticosterone administration resulted in a significant suppression. These results indicate that corticosterone can produce a shift towards a Th2 predominate response, possibly at the expense of Th1-mediated responses.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Stanulis
authors.forename: S D
authors.initials: SD
authors.lastname: Jordan
authors.forename: J A
authors.initials: JA
authors.lastname: Rosecrans
authors.forename: M P
authors.initials: MP
authors.lastname: Holsapple
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D000917:Antibody Formation / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D003345:Corticosterone / Q000378:metabolism / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009294:Narcotics / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009294:Narcotics; D003042:Cocaine; D003345:Corticosterone