title: Glutathione depletion in rats impairs T-cell and macrophage immune function.
abstract: Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.
authors.affiliation: Laboratory for Surgical Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115.
authors.forename: M K
authors.initials: MK
authors.lastname: Robinson
authors.forename: M L
authors.initials: ML
authors.lastname: Rodrick
authors.forename: D O
authors.initials: DO
authors.lastname: Jacobs
authors.forename: J D
authors.initials: JD
authors.lastname: Rounds
authors.forename: K H
authors.initials: KH
authors.lastname: Collins
authors.forename: I B
authors.initials: IB
authors.lastname: Saporoschetz
authors.forename: J A
authors.initials: JA
authors.lastname: Mannick
authors.forename: D W
authors.initials: DW
authors.lastname: Wilmore
mesh_terms: D000818:Animals; D003208:Concanavalin A; D016638:Critical Illness; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D005978:Glutathione / Q000737:chemistry / Q000172:deficiency* / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D005978:Glutathione