title: Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen.
abstract: Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b(+) cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell activities and on innate activities (granulocyte accumulation, NO production) as well. However, increases of spleen cell respiratory burst activity and IL-1β production were observed. Effects of lower cadmium doses (5ppm and 50ppm) on several aspects of spleen cell immune activity were observed in intermediate period of exposure (30 days, oral intake) as well. Differential effects of Cd on immune activities of spleen cells might contribute to our understanding of the complexity of immunomodulatory effects of this metal.
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Demenesku
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ninkov
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Popov Aleksandrov
authors.affiliation: Institute of Pathology, Military Medical Academy, 17Crnotravska 11000 Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Zolotarevski
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia; Institute of Zoology, Faculty of Biology, University of Belgrade, 16 Studentski trg, 11000 Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.affiliation: Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia; Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 16 Studentski trg, 11000 Belgrade, Serbia. Electronic address: milena@ibiss.bg.ac.rs.
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D019256:Cadmium Chloride
keywords: Cadmium; Inflammatory cytokines; Innate immunity; Rats; Spleen; T cell activity