Glutathione

Clin Invest Med, 12: 154-61, 1989

Immunoenhancing Property Of Dietary Whey Protein In Mice: Role Of Glutathione

G. Bounous, G. Batist, P. Gold

Montreal General Hospital, Quebec

ABSTRACT – The spleen cells immune response to sheep red blood cells of C3H/HeJ mice fed a 20 g whey protein/100 g diet is substantially higher than that of mice fed an equivalent casein diet of similar nutritional efficiency. The present study indicates that the observed immunoenhancing effect of the whey protein mixture is dependent on the overall amino acid pattern resulting from the contribution of all its protein components. Whey protein contains substantially more cysteine than casein. Dietary cysteine is considered to be a rate limiting substrate for the synthesis of glutathione which is necessary for lymphocyte proliferation. Our studies show that enhancement of host humoral immune response is associated with greater and more sustained production of splenic glutathione during the antigen driven clonal expansion of the lymphocyte in whey protein fed mice in comparison to mice fed the equivalent casein or the cysteine-enriched casein diet. Hence the efficiency of dietary cysteine in inducing supernormal glutathione levels is greater when it is delivered in the whey protein than as free cysteine. Administration of S-(n-butyl) homocysteine sulfoximine, which reduces splenic glutathione level by half, produces a 4-5 fold drop in the humoral immune response of whey protein diet-fed mice. This is further evidence of the important role of glutathione in the immunoenhancing effect of dietary whey protein.

Bounous G, Kongshavn PA, Gold P Montreal General Hospital Research Institute, Quebec, Canada."Mixing lactalbumin with either casein or soy protein in a 20 g protein/100 g diet formula significantly enhanced the immune response in comparison to that of mice fed diets containing 20% soy protein or casein."

Influence Of Dietary Lactalbumin Hydrolysate On The Immune System Of Mice And Resistance To Salmonellosis
G. Bounous, M.M. Stevenson, P.A.L. Kongshavn [The Journal of Infectious Diseases, 144: 281, 1981] Our data indicate that it was possible to increase the level of this type of protein in the diet above the minimum requirement and thus produce augmented humoral immune responsiveness and resistance to salmonellosis. Lactalbumin = Whey Protein Concentrate

Functions of glutathione and glutathione disulfide in immunology and immunopathology
Droge W, Schulze-Osthoff K, Mihm S, Galter D, Schenk H, Eck HP, Roth S, Gmunder H. [FASEB J. 1994 Nov;8(14):1131-8.] Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the immunologically important transcription factor NF kappa B, whereas high GSSG levels inhibit the DNA binding activity of NF kappa B. The effector phase of cytotoxic T cell responses and IL-2-dependent functions are inhibited even by a partial depletion of the intracellular GSH pool. As signal transduction is facilitated by prooxidant conditions, we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency. As HIV-infected patients and SIV-infected rhesus macaques have, on the average, significantly decreased plasma cyst(e)ine and intracellular GSH levels, we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well.

Effects of purified bovine whey factors on cellular immune functions in ruminants
Wong CW, Seow HF, Husband AJ, Regester GO, Watson DL. [Vet Immunol Immunopathol. 1997 May;56(1-2):85-96.] Alpha-lactalbumin (alpha LA) exhibited an enhancing effect on IL-1 beta production. As bovine whey fractions become progressively more purified, their modulatory effects on the immune response also become more clear-cut.

Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense
Villa P, Saccani A, Sica A, Ghezzi P. [J Infect Dis 2002 Apr 15;185(8):1115-20] Because glutathione (GSH) is lower in sepsis, the hypothesis that GSH depletion might impair the migratory response of neutrophils to infection was tested....GSH depletion inhibited peritoneal neutrophil infiltration, increased bacterial colonies, augmented pulmonary neutrophil infiltrate, and worsened survival. Conversely, the GSH precursor N-acetyl-l-cysteine augmented neutrophil infiltration in the peritoneum but not in the lung, decreased bacterial colonies, and improved survival. Thus, migration of neutrophils to a site of infection and to a distant site is differently regulated, and optimal GSH levels are important for an efficient response to sepsis.

Glutathione-induced enhancement of neutrophil locomotion
Elferink JG, de Koster BM. [Immunobiology 1991 Dec;184(1):25-36] Both reduced glutathione (GSH) and and its oxidized form, glutathione disulfide (GSSG), enhance neutrophil locomotion. The enhancement is mainly due to a chemokinetic effect, and partly due to a chemotactic effect. GSH enhances the intracellular concentration of cGMP, which might indicate that the effect on neutrophil locomotion is mediated by an effect on cGMP.