The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Proteolytic Enzymes and Amylase Induce Cytokine Production in Human Peripheral Blood Mononuclear Cells in vitro
Abstract
In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with proteolytic enzymes (bromelain, papain) and amylase leads to the production of large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-alpha and IL-6 production was already found after 4-6 hours of incubation, and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were observed. Control cultures contained below 35 pg/ml/10(6) PBMNC of TNF-alpha, IL-1 beta or IL-6. In contrast to TNF-alpha which was undetectable after more than 24 hours, peak levels of IL-1 beta and IL-6 were still present at 24 hours. After incubation of the enzyme solution for some hours at 56 degrees C the cytokine inducing capacity disappeared. Neutralization experiments with inactivating antibodies, radioimmunoassay, and western blotting after electrophoretic separation showed that the TNF-like activity found in the lytic assay was due to TNF-alpha. Interferon-alpha (IFN-alpha) and Interferon-gamma (IFN-gamma), which had no effect alone, synergistically increased TNF-alpha production when applied together with the enzymes. A commercial mixture of these enzymes (Wobenzym), which was also investigated, showed a similar concentration and time dependence, as well as synergism with the interferons. A synergisti…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“α -amylase serves a proxy for adrenergic activation, and adrenergic signaling is known to up-regulate proinflammatory cytokine production”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Desser, Rehberger, & Paukovits, 1994
Citations
Cites
An endotoxin-induced serum factor that causes necrosis of tumors
Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., & Williamson, B. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3666 · Cited by 4,532
Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF)
Akira, S., Hirano, T., Taga, T., & Kishimoto, T. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.11.2199284 · Cited by 1,306
Comparison of in vitro cell cytotoxic assays for tumor necrosis factor
Flick, D. A., & Gifford, G. E. (1984) · Journal of Immunological Methods · doi:10.1016/0022-1759(84)90147-9 · Cited by 738
Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update
Taussig, S. J., & Batkin, S. (1988) · Journal of Ethnopharmacology · doi:10.1016/0378-8741(88)90127-4 · Cited by 263
Degliantoni, G., Murphy, M., Kobayashi, M., Francis, M. K., PERUSSIA, B., & Trinchieri, G. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.162.5.1512 · Cited by 239
Okusawa, S., Yancey, K. B., van der Meer, J. W., Endres, S., Lonnemann, G., Hefter, K., Frank, M., Burke, J. F., Dinarello, C. A., & Gelfand, J. A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.168.1.443 · Cited by 213
Sung, S. S., Bjorndahl, J. M., Wang, C. Y., Kao, H., & Fu, S. M. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.3.937 · Cited by 185
Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells.
Sung, S. S., Jung, L. K. L., Walters, J. A., Chen, W., Wang, C. Y., & Fu, S. M. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.168.5.1539 · Cited by 166
Debets, J. M. H., van de Winkel, J. G. J., Ceuppens, J. L., Dieteren, I. E. M., & Buurman, W. A. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.4.1304 · Cited by 134
Cytokines: From clone to clinic
Aggarwal, B. B., & Pócsik, É. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90002-e · Cited by 69
Research works printed but not linked: 1
- 1976, Chemotherapy, 8, 517
Cited by
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Properties and Therapeutic Application of Bromelain: A Review
Pavan, R., Jain, S., Shraddha, S., & Kumar, A. (2012) · Biotechnology Research International · doi:10.1155/2012/976203 · Cited by 515
Potential role of bromelain in clinical and therapeutic applications
Rathnavelu, V., Alitheen, N. B., Sohila, S., Kanagesan, S., & Rajendran, R. (2016) · Biomedical Reports · doi:10.3892/br.2016.720 · Cited by 280
Bromelain’s activity and potential as an anti-cancer agent: Current evidence and perspectives
Chobotova, K., Vernallis, A. B., & Majid, F. A. A. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.08.001 · Cited by 219
Varilla, C., Marcone, M. F., Paiva, L. S., & Baptista, J. (2021) · Foods · doi:10.3390/foods10102249 · Cited by 185
Mohamed, S. I. A., Jantan, I., & Haque, M. A. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.07.010 · Cited by 140
Bromelain: A Literature Review and Discussion of its Therapeutic Applications
Kelly, G. S. (1996) · Cited by 114
Bromelain Modulates T Cell and B Cell Immune Responses in Vitro and in Vivo
Engwerda, C. R., Andrew, D., Ladhams, A., & Mynott, T. L. (2001) · Cellular Immunology · doi:10.1006/cimm.2001.1807 · Cited by 104
Short-Term Treatment of Painful Osteoarthritis of the Knee with Oral Enzymes
Klein, G., & Kullich, W. (2000) · Clinical Drug Investigation · doi:10.2165/00044011-200019010-00003 · Cited by 84
Bromelain Activates Murine Macrophages and Natural Killer Cells in Vitro
Engwerda, C. R., Andrew, D., Murphy, M. L., & Mynott, T. L. (2001) · Cellular Immunology · doi:10.1006/cimm.2001.1793 · Cited by 74
Insuan, O., Janchai, P., Thongchuai, B., Chaiwongsa, R., Khamchun, S., Saoin, S., Insuan, W., Pothacharoen, P., Apiwatanapiwat, W., Boondaeng, A., et al. (2021) · Current Issues in Molecular Biology · doi:10.3390/cimb43010008 · Cited by 64
Anticancer Property of Bromelain With Therapeutic Potential in Malignant Peritoneal Mesothelioma
Pillai, K., Akhter, J., Chua, T. C., & Morris, D. L. (2013) · Cancer Investigation · doi:10.3109/07357907.2013.784777 · Cited by 58
Grzonka, Z., Kasprzykowski, F., & Wiczk, W. M. (2007) · Springer eBooks · doi:10.1007/1-4020-5377-0_11 · Cited by 58
Barth, H., Guseo, A., & Klein, R. (2005) · PubMed · Cited by 55
Wali, N. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812491-8.00050-3 · Cited by 54
Bottega, R., Persico, I., Seta, F. D., Romano, F., & Lorenzo, G. D. (2021) · International Journal of Immunopathology and Pharmacology · doi:10.1177/20587384211034686 · Cited by 39
Závadová, E., Desser, L., & Mohr, T. T. (1995) · Cancer Biotherapy · doi:10.1089/cbr.1995.10.147 · Cited by 31
Self-citationBacoside A and bromelain relieve dichlorvos induced changes in oxidative responses in mice serum
Agarwal, S., Chaudhary, B., & Bist, R. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.05.017 · Cited by 30
Bromelain supplementation and inflammatory markers: A systematic review of clinical trials
Pereira, I. C., Vieira, E. E. S., Torres, L. R. D. O., da Silva, F. C. C., Sousa, J. M. D. C. E., & Torres‐Leal, F. L. (2023) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2023.02.028 · Cited by 28
Bromelain has paradoxical effects on blood coagulability
Kaur, H., Corscadden, K., Lott, C., Elbatarny, H. S., & Othman, M. (2015) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000000244 · Cited by 25
Rumbus, Z., Tóth, E., Pótó, L., Vincze, Á., Veres, G., Czakó, L., Olah, E., Márta, K., Mikó, A., Rakonczay, Z., et al. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01360 · Cited by 24
Mahajan, S., Chandra, V., Dave, S., Nanduri, R., & Gupta, P. K. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis354 · Cited by 24
Dose-dependent induction of IL-6 by plant-derived proteasesin vitro
Rose, B., Herder, C., Löffler, H., Meierhoff, G., Schloot, N. C., Walz, M., & Martin, S. (2005) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2005.02970.x · Cited by 23
Oral immunogenicity of the plant proteinase bromelain
Hale, L. P., Fitzhugh, D. J., & Staats, H. F. (2006) · International Immunopharmacology · doi:10.1016/j.intimp.2006.08.007 · Cited by 23
Rahayu, P., Agustina, L., & Tjandrawinata, R. R. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12241 · Cited by 19
Bartel, M. J., Hänsch, G., Giese, T., Penzel, R., Ceyhan, G., Ketterer, K., von Knebel-Döberitz, M., Friess, H., & Giese, N. (2008) · The Journal of Pathology · doi:10.1002/path.2348 · Cited by 17
Gomes, M. T. R., Turchetti, A., Lopes, M. T. P., & Salas, C. E. (2009) · Biological Chemistry · doi:10.1515/bc.2009.137 · Cited by 12
Over-the-Counter Enzyme Supplements: What a Clinician Needs to Know
Varayil, J. E., Bauer, B. A., & Hurt, R. T. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.05.015 · Cited by 11
Bromelain in Obesity Therapy: A Review of Anti-Inflammatory and Metabolic Mechanisms
Sethia, Y., Polak-Szczybyło, E., & Tabarkiewicz, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178347 · Cited by 10
Evaluating the effect of oral bromelain (pineapple) on episiotomy wound healing in primiparus women
Golozar, S., Abbaspour, Z., Namjouyan, F., Latifi, S. M., & Mirahi, A. (2011) · KAUMS Journal · Cited by 9
Nutrition, Immunity, and Cancer
Ghaedi, E., Rezaei, N., & Mahmoudi, M. (2019) · Springer eBooks · doi:10.1007/978-3-030-16073-9_12 · Cited by 9
Exogenous Proteases Confer a Significant Chemopreventive Effect in Experimental Tumor Models
Wald, M. (2008) · Integrative Cancer Therapies · doi:10.1177/1534735408327036 · Cited by 8
Therapeutic Application of Pineapple: A Review
Kumar, V., Garg, V., & Dureja, H. (2023) · Recent Advances in Food Nutrition & Agriculture · doi:10.2174/2772574x14666230522114039 · Cited by 7
HLA-DQ8 is a predisposing molecule for detergent enzyme subtilisin BPN′-induced hypersensitivity
Xue, A., Chapoval, S. P., Finn, E. S., CHOWDHARY, V. R., Marietta, E. V., Gaffey, T. A., Pursifull, A. C., & David, C. S. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.08.003 · Cited by 6
Amini, A., Masoumi-Moghaddam, S., & Morris, D. L. (2016) · Springer eBooks · doi:10.1007/978-3-319-28570-2_3 · Cited by 4
Emerging trends in extraction and analytical techniques for bromelain
Maheshwari, D., Shah, J. S., Shah, D. B., Patel, P. K., & Singh, Y. R. (2022) · Journal of Liquid Chromatography & Related Technologies · doi:10.1080/10826076.2022.2161573 · Cited by 4
Assessment of Some Biomarkers in Liver, Kidney and Stomach Following Pineapple Juice Administration
Oyesola, T. O., Oyesola, O., Odukoya, S. O. A., & Adelodun, S. T. (2016) · International Journal of Pharmacology Phytochemistry and Ethnomedicine · doi:10.18052/www.scipress.com/ijppe.4.27 · Cited by 3
Adjuvant Therapy with Hydrolytic Enzymes in Recurrent Laryngeal Papillomatosis
Mudrák, J., Bobák, L., & Šebová, I. (1997) · Acta Oto-Laryngologica · doi:10.3109/00016489709124054 · Cited by 2
Delgarm, P., Mokhtare, M., Daryani, N. E., Abolghasemi, J., & Rahideh, S. T. (2025) · Scientific Reports · doi:10.1038/s41598-025-26975-1 · Cited by 1
Wald, M., Závadová, E., POUCKOVA, P., Zadinová, M., & Boubelík, M. (1997) · Life Sciences · doi:10.1016/s0024-3205(97)01106-5 · Cited by 1
Complementary and Alternative Medicine in Rhinology
Antunes, M. B., Tamashiro, E., & Cohen, N. A. (2008) · Springer eBooks · doi:10.1007/978-0-387-73062-2_9
Response by Robinson, Wan and Winton
Робинсон, Wan, & Winton (1999) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1999.0533b.x
Secor, E. R. (2003) · Techniques in Orthopaedics · doi:10.1097/00013611-200303000-00011
ENZYME SUPPLEMENTS EFFECTIVENESS and BENEFITS in NUTRITION and HEALTH
Mamadou, M. N. (2015)
Important therapeutic targets in acute pancreatitis
Tóth, E. (2019) · SZTE Repository of Dissertations (University of Szeged) · doi:10.14232/phd.10329
Phadnis, A. (2023) · Diva portal (Dalarna University Library)
Metadata
- Authors
- Desser, L., Rehberger, A., & Paukovits, W.
- Affiliations
- University of Vienna (AT)
- Venue
- Cancer Biotherapy
- Publisher
- SAGE Publications
- Published
- 1994-01
- Volume
- 9
- Issue
- 3
- Pages
- 253-263
- ISSN
- 1062-8401 (ISSN-L)
- OpenAlex
- W2091127196
- Cited by
- 45
- References
- 12
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Biotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- proteolytic enzymes, bromelain, papain, amylase, peripheral blood mononuclear cells, cytokine production, TNF-α, IL-1β, interleukin-6, interferon-alpha, interferon-gamma, enzyme synergy, phorbol ester, Wobenzym
- MeSH terms
- Amylases, Bromelains, Cells, Cultured, Drug Synergism, Gene Expression Regulation, Humans, Interferons, Interleukin-1, Leukocytes, Mononuclear, Papain, Tetradecanoylphorbol Acetate, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review