title: Effects of an illicit cocktail on serum immunoglobulins, lymphocyte proliferation and cytokine gene expression in the veal calf.
abstract: At the European Union level, the use of growth promoters (GPs) in cattle and other food-producing species is forbidden; nonetheless, the illicit use of anabolic hormones, beta-agonists and corticosteroids, often administered in cocktails at lower concentrations to overcome control procedures, is still of public concern. The immune system (IS) is a multicomponent system that provide a coordinated response toward infectious diseases, not self-neoplasms and xenobiotics; in this respect, some GPs have been proved able to cause both morphological alterations in lymphoid organs and a modulating effect upon some immunological parameters. Therefore, in the present study the effects of an illicit cocktail upon the cattle IS functions were investigated by using some common endpoints adopted for the IS testing in humans. Twelve cross-bred male veal calves were divided in two experimental groups (n=6); the first group was administered a cocktail of 17beta-oestradiol (10 mg, 3 im injections at 17 days intervals), clenbuterol (20 microg kg(-1), per os for 40 days) and dexamethasone (4 mg per os for 6 days and, then, 5mg for further 6 days) for a total of 55 days. The second one was used as control. Blood sampling were taken at T(0) and after 15 (T(1)), 34 (T(2)), 48 (T(3)) days as well as the day before slaughtering (T(4)). Immune endpoints considered were the thymus weight, the serum immunoglobulin G (IgG) and M (IgM) levels, the lymphocyte proliferation assay and the lymphocyte interleukins 1beta and 8, tumour necrosis factor alpha and interferon gamma (IFN-gamma) gene expression levels. The administration of the illicit cocktail resulted in: (a) a reduction (P<0.01) of both the absolute and relative thymus weight; (b) a decrease (P<0.05) of both IgG and IgM serum levels at T(1), whereas in the second part of the study increasing levels (P<0.05 at T(2) and T(4) for IgM and IgG, respectively) were recorded; (c) an overall reduction (P<0.001, P<0.05) of lymphocyte proliferation rate at T(1); in phytohaemagglutinin-stimulated cells, such a decrease was delayed up to T(2) (P<0.05); (d) a reduction (P<0.05) in IFN-gamma mRNA levels at T(1) and T(2). Taken together, present data suggest that GPs, even given in cocktails at sub-therapeutic dosages, can modulate the cattle IS, thereby hampering itself to exert its physiological role in defence mechanisms. Further studies are required to confirm and investigate these results.
authors.affiliation: Dipartimento di Patologia Animale, sezione di Farmacologia e Tossicologia, Università di Torino, via Leonardo da Vinci 44, I-10095, Grugliasco, Torino, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cantiello
authors.forename: Monica
authors.initials: M
authors.lastname: Carletti
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Cannizzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Nebbia
authors.forename: Claudio
authors.initials: C
authors.lastname: Bellino
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pié
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
authors.forename: Enrico
authors.initials: E
authors.lastname: Bollo
authors.forename: Mauro
authors.initials: M
authors.lastname: Dacasto
mesh_terms: D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D045930:Anabolic Agents / Q000494:pharmacology; D000822:Animal Husbandry; D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation / Q000187:drug effects*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002976:Clenbuterol / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D013287:Illicit Drugs / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008460:Meat; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D045930:Anabolic Agents; D016207:Cytokines; D005938:Glucocorticoids; D006133:Growth Substances; D013287:Illicit Drugs; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D003907:Dexamethasone; D007371:Interferon-gamma; D002976:Clenbuterol