title: Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.
abstract: Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.
authors.affiliation: Immunology Centre, Research Department, Institute National Research Centres on Aging, Ancona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: A
authors.initials: A
authors.lastname: Ciavattini
authors.forename: L
authors.initials: L
authors.lastname: Santarelli
authors.forename: A
authors.initials: A
authors.lastname: Tibaldi
authors.forename: M
authors.initials: M
authors.lastname: Muzzioli
authors.forename: P
authors.initials: P
authors.lastname: Bonazzi
authors.forename: R
authors.initials: R
authors.lastname: Giacconi
authors.forename: N
authors.initials: N
authors.lastname: Fabris
authors.forename: G G
authors.initials: GG
authors.lastname: Garzetti
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000097:blood*; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000097:blood; D013935:Thymic Factor, Circulating / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology*; D015032:Zinc / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000502:physiology*
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000511:alpha-Macroglobulins; D013935:Thymic Factor, Circulating; D015032:Zinc