1.
Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers.
Bose, N, Ottoson, NR, Qiu, X, Harrison, B, Lowe, JR, Uhlik, MT, Rathmann, BT, Kangas, TO, Jordan, LR, Ertelt, KE, et al
Journal of immunology (Baltimore, Md. : 1950). 2019;(10):2945-2956
Abstract
Imprime PGG (Imprime) is an i.v. administered, yeast β-1,3/1,6 glucan in clinical development with checkpoint inhibitors. Imprime-mediated innate immune activation requires immune complex formation with naturally occurring IgG anti-β glucan Abs (ABA). We administered Imprime to healthy human volunteers to assess the necessity of ABA for Imprime-mediated immunopharmacodynamic (IPD) changes. Imprime (4 mg/kg) was administered i.v. in single and multiple infusions. Subsets of subjects were premedicated with antihistamine and corticosteroid. Peripheral blood was measured before, during and after Imprime administration for IPD changes (e.g., ABA, circulating immune complexes, complement activation, complete blood counts, cytokine/chemokine, and gene expression changes). IPD changes were analyzed based on pretreatment serum ABA levels: low-ABA (<20 μg/ml), mid-ABA (≥20-50 μg/ml), and high-ABA (≥50 μg/ml). At the end of infusion, free serum ABA levels decreased, circulating immune complex levels increased, and complement activation was observed. At ∼1-4 h after end of infusion, increased expression of cytokines/chemokines, a 1.5-4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed. Low-ABA subjects typically showed minimal IPD changes except when ABA levels rose above 20 μg/ml after repeated Imprime dosing. Mild-to-moderate infusion-related reactions occurred in subjects with ABA ≥20 μg/ml. Premedications alleviated some of the infusion-related reactions, but also inhibited cytokine responses. In conclusion, ABA levels, being critical for Imprime-mediated immune activation may provide a plausible, mechanism-based biomarker to identify patients most likely to respond to Imprime-based anticancer immunotherapy.
2.
Baker's yeast β-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?
Carpenter, KC, Breslin, WL, Davidson, T, Adams, A, McFarlin, BK
The British journal of nutrition. 2013;(3):478-86
Abstract
Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast β-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of β-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.
3.
New perspectives in the treatment of hidradenitis suppurativa: surgery and brewer's yeast-exclusion diet.
Cannistrà, C, Finocchi, V, Trivisonno, A, Tambasco, D
Surgery. 2013;(5):1126-30
Abstract
BACKGROUND Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory skin disease characterized by abscesses, fistulating sinus tracts, and scarring. The exact pathogenesis of this disease remains unclear. We present our experience with HS and a possible cause of the disease and offer a surgical and clinical treatment that allows for disease resolution. METHODS We studied 12 patients who presented with axillary and perineal fistulas and underwent surgical excision (repaired by skin grafts or healing by secondary intention) or localized treatments followed by diet modification. All patients were found to have a specific immunology IgG reaction to brewer's yeast and wheat and were put on a controlled brewer's yeast-free diet for 12 months and followed monthly. RESULTS The diet demonstrated immediate stabilization of their clinical symptoms, and the skin lesions regressed over the 12-month treatment period. Similarly, all the patients demonstrated an immediate recurrence of skin lesions following accidental or voluntary consumption of beer or other foods containing brewer's yeast or wheat. The patients also demonstrated a return of their quality of life and activities, including the reestablishment of sexual activity in the patients with inguinal and perigenital lesions. CONCLUSION The results of the investigation suggested that the patients had severe reactions to brewer's yeast. Surgery followed by the elimination of the foods containing or made with the yeast resulted in a rapid stabilization of the dermatologic manifestation and a slow, but complete, regression of the skin lesions within a year. Despite the small number of patients in our study, our study could provide the basis for extensive and multicentric studies in order to better investigate this disabling and rare disease.
4.
Chemical composition and anti-stress effects of yeast hydrolysate.
Lee, HS, Jung, EY, Suh, HJ
Journal of medicinal food. 2009;(6):1281-5
Abstract
In the present study, the anti-stress effects of yeast hydrolysate (YH) were investigated. The YH consisted of crude carbohydrate (23.6%) and crude protein (68.3%) with low contents of crude ash (3.1%) and crude fat (0.3%). Also, acidic amino acids (glutamic acid + aspartic acid) were present in large quantities (14.2 and 5.0 mol%, respectively). Pronase digestion had little effect on the affinity of the YH on 5-hydroxytryptamine (serotonin) and norepinephrine transporters, whereas NaIO(4) oxidation of the hydrolysate decreased the affinity by about 10% at 1,000 microg/mL, indicating that the periodate-labile carbohydrate moiety played a leading role in the affinity effects of the carbohydrate in YH. As a result of brain mapping after the administration of the YH for 3 days in human subjects, a symmetrical distribution of theta and alpha waves in the central and parietal lobes was observed. This brain mapping pattern of theta and alpha wave distribution appears in a psychologically stable state. The YH groups showed improvements in Beck Depression Inventory and Beck Anxiety Inventory scores after YH administration for 2 weeks. Treatment also seemed to have a more significant (P < .05) impact on the somatic manifestations of anxiety as indexed by the Beck Anxiety Inventory scores. Food materials used as a source of YH have been found to be associated with increases in alertness and adaptation to stress.
5.
Saccharomyces boulardii in Crohn's disease: effect on anti-Saccharomyces cerevisiae antibodies and intestinal permeability.
Joossens, S, Suenaert, P, Noman, M, Vermeire, S, Rutgeerts, P
Inflammatory bowel diseases. 2005;(9):863-4