Bromelain Activates Murine Macrophages and Natural Killer Cells in Vitro

Engwerda, Christian; Andrew, Deborah; Murphy, Marianne; Mynott, Tracey L.

doi:10.1006/cimm.2001.1793

Cited by 61 publications

(37 citation statements)

References 28 publications

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“…However, the net effect of bromelain treatment may depend on the activity of specific proteinases within the bromelain preparations used (29) as well as on the complement of bromelain-sensitive cell surface molecules expressed by the treated cells. Published studies have shown mixed effects of bromelain on activation and cytokine secretion by leukocytes (3,19,20,30,31) and colon epithelial cells (21). We found no significant decreases in the levels of pro-inflammatory cytokines in the peritoneal lavage fluid of bromelain-treated mice.…”

Section: Discussioncontrasting

confidence: 61%

“…The majority of inflammatory cells present in the peritoneal cavity at the time of our analysis were neutrophils and resident macrophages. Others have also reported activation of macrophage cytokine secretion by bromelain (30). We hypothesize that the net effect of bromelain in any given biologic situation depends on the cell types present, since each cell type may express different relative numbers of bromelain-sensitive pro-inflammatory vs. anti-inflammatory surface molecules and thus have differing net biologic responses to their proteolytic removal.…”

Section: Discussionmentioning

confidence: 84%

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Bromelain treatment decreases neutrophil migration to sites of inflammation

Fitzhugh

Shan

Dewhirst

et al. 2008

Clinical Immunology

116

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Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain-vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 -85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 84%

Bromelain treatment decreases neutrophil migration to sites of inflammation

Fitzhugh

Shan

Dewhirst

et al. 2008

Clinical Immunology

116

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“…In previous reports, experiments were often limited to isolated cell types or unphysiologically stimulated lymphocyte cultures Bromelain + PmB treated with high doses of single proteases, usually resulting in protease-mediated increase of cytokine expression [4][5][6]. The MMLC system represents an ex vivo approach to determine immunomodulatory effects not only on single cell level, but also on the interplay between different kinds of immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that protease treatment can induce or enhance release of cytokines as well as nitric oxide from leucocytes in vitro [4][5][6] and that oral doses of proteases also influence cytokine expression in vivo [7,8]. Protease treatment does however not always entail immune stimulation.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent induction of IL-6 by plant-derived proteasesin vitro

Rose

Herder

Löffler

et al. 2005

Clinical and Experimental Immunology

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SummaryOral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNγ γ γ γ and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction.

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“…Bromelain was recommended as a supportive therapeutic approach during the treatment of chronic inflammatory, malignant and auto-immune disease [16]. Animal in-vitro experiment showed its ability to modulate surface adhesion of T cells, macrophages and natural killer cells among others [17][18][19][20][21][22][23]. It was reported that fruits and vegetables consumption promotes good health; therefore, wide publicity and recommendation were given for their consumption because they have been implicated for their health promoting properties in most developed countries [24].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Some Biomarkers in Liver, Kidney and Stomach Following Pineapple Juice Administration

Oyesola

et al. 2016

IJPPE

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Abstract. This study looked into the physiochemical assessment of kidney, liver and stomach following pineapple juice (PJ) administration in normal Wistar rats. Thirty-two young male Wistar rats weighing between 180 -200 g were used for this study. The juice was administered through oral cannula for 30 days. The animals were grouped into four (A-D). Group A received 3 ml of distilled water (Control), Group B received 3 ml/kg PJ, Group C received 6 ml/kg PJ administered at 3 ml twice daily and Group D received 9 ml/kg PJ at 3 ml three times daily for one month. Blood samples were collected a day post-administration through cardiac puncture for hematological and biochemical studies. Mucosal tissues were scraped from the stomach and homogenized to check for total protein and some other gastric enzymes. The study showed a significant decrease (P < 0.05) in cholesterol and triglycerides (113.4 ± 1.60-104.4 ± 1.66 and 104.4 ± 1.66-74.0 ± 2.95) while low density and high density lipoproteins showed no significant difference. Electrolyte concentrations of sodium, potassium, chloride, bicarbonate, urea and creatinine showed significant decreases. Liver enzyme parameters were significantly increased (P > 0.05) for ALP (40.0 ± 4.05 -79.4 ± 6.61 IU/L), AST (115.2 ± 1.46-178.4 ± 2.00 IU/L), ALT (86.0 ± 2.68-72.2 ± 3.90 IU/L) and ALB (3.16 ± 0.09 -3.84 ± 0.02 IU/L). Results of Total Protein showed a significant increase while bilirubin is insignificantly different compared with the control. Results for SOD, TBAR, CATAL and MDA showed no significant differences. The study revealed that the hematological parameters assayed: Hb (11.85 ± 2.0 -14.12 ± 1.5 g/100 ml), RBC count (6.27 ± 0.1-9.92 ± 1.5×10 6 /mm3) and Total WBC counts (2.35 ± 0.6 -4.47 ± 0.5 × 103/mm3) were significantly higher (P < 0.05). We concluded that the oral administration of PJ to Wistar rats for one month is beneficial by reducing cholesterol level and some toxic gastric enzymes. It also increased hematopoietic outputs, and served as an immune booster judging from the Total WBC count results while its effect on liver function is minimal based on this present study.

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Bromelain Activates Murine Macrophages and Natural Killer Cells in Vitro

Cited by 61 publications

References 28 publications

Bromelain treatment decreases neutrophil migration to sites of inflammation

Bromelain treatment decreases neutrophil migration to sites of inflammation

Dose-dependent induction of IL-6 by plant-derived proteasesin vitro

Assessment of Some Biomarkers in Liver, Kidney and Stomach Following Pineapple Juice Administration

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