Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model
Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each yea...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/13/7/2366 |
| _version_ | 1797526373590368256 |
|---|---|
| author | Annie Lauer Markus Burkard Heike Niessner Christian Leischner Olga Renner Claudia Vollbracht Holger Michels Christian Busch Tobias Sinnberg Sascha Venturelli |
| author_facet | Annie Lauer Markus Burkard Heike Niessner Christian Leischner Olga Renner Claudia Vollbracht Holger Michels Christian Busch Tobias Sinnberg Sascha Venturelli |
| author_sort | Annie Lauer |
| collection | DOAJ |
| description | Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials. |
| first_indexed | 2024-03-10T09:29:18Z |
| format | Article |
| id | doaj.art-33951dfa22214a108cb2dd0cc52addf6 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T09:29:18Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-33951dfa22214a108cb2dd0cc52addf62023-11-22T04:36:27ZengMDPI AGNutrients2072-66432021-07-01137236610.3390/nu13072366Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) ModelAnnie Lauer0Markus Burkard1Heike Niessner2Christian Leischner3Olga Renner4Claudia Vollbracht5Holger Michels6Christian Busch7Tobias Sinnberg8Sascha Venturelli9Division of Dermatooncology, Department of Dermatology, University of Tübingen, 72076 Tübingen, GermanyInstitute of Nutritional Sciences, Nutritional Biochemistry, University of Hohenheim, 70599 Stuttgart, GermanyDivision of Dermatooncology, Department of Dermatology, University of Tübingen, 72076 Tübingen, GermanyInstitute of Nutritional Sciences, Nutritional Biochemistry, University of Hohenheim, 70599 Stuttgart, GermanyInstitute of Nutritional Sciences, Nutritional Biochemistry, University of Hohenheim, 70599 Stuttgart, GermanyPascoe Pharmazeutische Praeparate GmbH, 35394 Giessen, GermanyPascoe Pharmazeutische Praeparate GmbH, 35394 Giessen, GermanyDermatologie zum Delfin, 8400 Winterthur, SwitzerlandDivision of Dermatooncology, Department of Dermatology, University of Tübingen, 72076 Tübingen, GermanyInstitute of Nutritional Sciences, Nutritional Biochemistry, University of Hohenheim, 70599 Stuttgart, GermanySepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials.https://www.mdpi.com/2072-6643/13/7/2366vitamin Cvitamin B1hydrocortisonesepsiscytokine release |
| spellingShingle | Annie Lauer Markus Burkard Heike Niessner Christian Leischner Olga Renner Claudia Vollbracht Holger Michels Christian Busch Tobias Sinnberg Sascha Venturelli Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model Nutrients vitamin C vitamin B1 hydrocortisone sepsis cytokine release |
| title | Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model |
| title_full | Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model |
| title_fullStr | Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model |
| title_full_unstemmed | Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model |
| title_short | Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model |
| title_sort | ex vivo evaluation of the sepsis triple therapy high dose vitamin c in combination with vitamin b1 and hydrocortisone in a human peripheral blood mononuclear cells pbmcs model |
| topic | vitamin C vitamin B1 hydrocortisone sepsis cytokine release |
| url | https://www.mdpi.com/2072-6643/13/7/2366 |
| work_keys_str_mv | AT annielauer exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT markusburkard exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT heikeniessner exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT christianleischner exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT olgarenner exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT claudiavollbracht exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT holgermichels exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT christianbusch exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT tobiassinnberg exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel AT saschaventurelli exvivoevaluationofthesepsistripletherapyhighdosevitamincincombinationwithvitaminb1andhydrocortisoneinahumanperipheralbloodmononuclearcellspbmcsmodel |