Pentoxifylline as a Potential Adjuvant Therapy for COVID-19: Impeding the Burden of the Cytokine Storm

Feret, Wiktoria; Nalewajska, Magdalena; Wojczyński, Łukasz; Witkiewicz, Wojciech; Kłos, Patrycja; Dziedziejko, Violetta; Pawlik, Andrzej

doi:10.3390/jcm10225305

Cited by 9 publications

(4 citation statements)

References 60 publications

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“…Oxygenation and O2 saturation were significantly improved compared before and after the treatment in both intervention and control groups. The anti-inflammatory and immunomodulatory properties of PTX decrease the risk of ARDS in COVID-19 patients with significant lung involvement [26,31,32]. On top of that, pentoxifylline was reported to be beneficial in controlling the hypercoagulable state resulting from virus-induced injury to the epithelium [26,31,33].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Oral Pentoxifylline in the Treatment and Recovery of Patients with Moderate to Severe COVID-19 Infection Treated with Routine Protocols: A Randomized Controlled Clinical Trial

Seirafianpour

Almasi

Sadeghi

et al. 2023

Preprint

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Backgrounds: The absence of a gold-standard treatment for COVID-19 infection encourages clinicians to benefit from multipotential medications in the treatment of COVID-19. The current controlled randomized clinical trial tried to evaluate the efficacy and safety of pentoxifylline (PTX) as an adjuvant therapy in moderate to severe COVID-19 infection. Methods: In this randomized controlled clinical trial, two groups of hospitalized patients with moderate to severe COVID-19 infection were randomized by the block randomization method to either receive standard protocol therapy or standard protocol therapy plus pentoxifylline 400 mg TDS for 14 days. Results: The results showed a greater improvement in the proinflammatory biomarkers in the intervention group. Oxygen saturation, hemoglobin, and platelet levels were also improved to a higher level among pentoxifylline recipients. The mortality rate was reported 4% and 32% in the intervention and control groups, respectively. One out 13 patients with severe COVID-19 infection expired in the intervention group, while 20 out of 28 patients expired in the control group, showing about 10 times higher mortality rate compared to the pentoxifylline recipients. Conclusion: Pentoxifylline increased the survival rate of COVID-19 patients and played as a preventive role for COVID-related mortality and morbidity such as acute respiratory distress syndrome.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Oral Pentoxifylline in the Treatment and Recovery of Patients with Moderate to Severe COVID-19 Infection Treated with Routine Protocols: A Randomized Controlled Clinical Trial

Seirafianpour

Almasi

Sadeghi

et al. 2023

Preprint

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“…The effectiveness of pentoxifylline has been identified in the treatment of various lung diseases, including infectious causes. This drug has also been shown to reduce pulmonary fibrosis in patients with COVID-19 [28,29].…”

Section: Discussionmentioning

confidence: 99%

Gas Exchange in Patients with Pulmonary Tuberculosis: Relationships with Pulmonary Poorly Communicating Fraction and Alveolar Volume

Kiryukhina

Kokorina

Gavrilov

et al. 2023

JoR

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Tuberculosis-related lung damage is very different. Lung ventilation disorders have been studied in patients with pulmonary tuberculosis (TB) during the active process and after treatment, but the main causes of gas exchange changes have not been sufficiently studied. Investigation of diffusing lung capacity in combination with bodyplethysmography is useful for the interpretation of pulmonary gas exchange disorders. The aim was to determine the relationship of gas exchange with the value of alveolar volume (VA) and pulmonary poorly communicating fraction (PCF) in patients with pulmonary TB. A total of 292 patients (117/175 M/W) with verified pulmonary TB with smoking age less than 10 packs-years underwent spirometry, bodyplethysmography, and DLCO by the single-breath method. PCF was estimated calculating the difference between total lung capacity (TLC) and VA (% TLC). Patients with low DLCO had statistically significantly lower spirometric values (FVC, FEV1, FEV1/FVC, MMEF), lower TLC, higher airway resistance, RV/TLC, air-trapping volume, and PCF. The patients with low level of DLCO were divided into four groups depending on level VA and PCF. In most patients with infiltrative tuberculosis (50%), the leading syndrome of the DLCO decrease was alveolar-capillary damage. In patients with tuberculomas, the syndromes of alveolar capillary damage and pulmonary ventilation inhomogeneity were with the same frequency (43%). In patients with disseminated tuberculosis, the most frequent syndrome of the DLCO decrease was pulmonary ventilation inhomogeneity (33%), then alveolar-capillary damage (29%) and mixed (24%). In patients with cavernous tuberculosis, the leading syndrome of the DLCO decrease was mixed (39%), then alveolar capillary damage (25%) and pulmonary ventilation inhomogeneity (23%). The syndrome of gas exchange surface reduction in patients with disseminated and cavernous tuberculosis was less common (14%). In conclusion, an additional evaluation of the combination of PCF and VA increases the amount of clinical information obtained using the diffusion lung capacity measurements, since it allows identifying various syndromes of gas exchange impairment. The leading causes of diffusing capacity impairment vary by different types of pulmonary TB.

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“…PTX has also been shown to reduce IL-6, TNFα, CRP, and MCP-1 in other diseases such as in non-alcoholic steatohepatitis patients (21) and Cirrhosis (22) and was proposed as an adjunctive therapy in patients with irritable bowel syndrome (23) and in preterm neonates with suspected late onset sepsis (24). PTX is included in the preliminary drugs used for the treatment of the recent global pandemic COVID-19 (25)(26)(27)(28)(29). It has recently been published that part of COVID-19 pathology is the initiation of a "cytokine storm", which is especially apparent in severe forms of the disease.…”

Section: Discussionmentioning

confidence: 99%

PTX Treatment of Colon Cancer: Mode of Action Based on Tumor Marker and Cytokine Kinetics

et al. 2022

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Background/Aim: Cancer progression is associated with significant cachexia-induced weight loss and stomatitis. Pentoxifylline (PTX) is a drug shown to have beneficial antiinflammatory effects in cancer patients, mainly through anti-TNFα mechanisms. This study determined the PTX effects and mode of action on weight-loss, stomatitis, and survival in colon cancer patients treated with chemotherapy, examining the kinetics of tumor markers and cytokine levels. Patients and Methods: Forty patients with metastatic colon cancer receiving chemotherapy, were randomized in this study. Seventeen patients were assigned to the treatment group -8 received a full PTX dose (400 mg TID) and 9 a reduced dose (200 mg TID). Results were compared to 23 untreated, control patients. Blood analysis of tumor markers (CEA and TPS), inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα, TNF-R), CRP and sIL-2R, were performed. Additionally, clinical parameters were assessed. Results: Patients treated with PTX (full/reduced doses), gained significant weight, and experienced a reduction in stomatitis, resulting in multiple beneficial effects, including improved life quality. Significant reductions in CRP, sIL-2R, and inflammatory cytokine levels, correlated to increases in weight and a reduction in stomatitis. A similar pattern was observed in tumor marker levels, where decreasing levels were correlated with weight gain and reduction in inflammatory cytokine levels. Conclusion: Colon cancer patients receiving PTX with chemotherapy, experienced weight gain and reduced stomatitis occurrence. Beneficial PTX effects were correlated to significant decreases in patient inflammatory cytokines and tumor marker levels, probably due to PTX mode of action.

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Pentoxifylline as a Potential Adjuvant Therapy for COVID-19: Impeding the Burden of the Cytokine Storm

Cited by 9 publications

References 60 publications

Efficacy and Safety of Oral Pentoxifylline in the Treatment and Recovery of Patients with Moderate to Severe COVID-19 Infection Treated with Routine Protocols: A Randomized Controlled Clinical Trial

Efficacy and Safety of Oral Pentoxifylline in the Treatment and Recovery of Patients with Moderate to Severe COVID-19 Infection Treated with Routine Protocols: A Randomized Controlled Clinical Trial

Gas Exchange in Patients with Pulmonary Tuberculosis: Relationships with Pulmonary Poorly Communicating Fraction and Alveolar Volume

PTX Treatment of Colon Cancer: Mode of Action Based on Tumor Marker and Cytokine Kinetics

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