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Pentoxifylline fails to prevent the Jarisch-Herxheimer reaction or associated cytokine release
D G Remick1, Y Negussie, D Fekade
1Department of Pathology, University of Michigan, Ann Arbor, USA.
Abstract:
The Jarisch-Herxheimer reaction (JHR) observed after antibiotic treatment of relapsing fever caused by Borrelia recurrentis is associated with the systemic appearance of cytokines. The decrease of cytokine production and block of JHR was attempted by administering pentoxifylline prior to antibiotic treatment. Fifteen patients with confirmed relapsing fever were infused intravenously with pentoxifylline 90 min before intramuscular injection of penicillin; 4 patients were not treated with pentoxifylline. All patients developed JHR to varying degrees. Treatment with pentoxifylline failed to prevent fever, increase in pulse, respiration, or blood pressure, or decrease in white blood cell count. No reduction of circulating levels of tumor necrosis factor, interleukin 6, or interleukin-8 was observed with pentoxifylline treatment. Pentoxifylline did not prevent clearance of the B. recurrentis spirochetes. Thus, pentoxifylline treatment of patients with relapsing fever fails to prevent or diminish JHR or the associated cytokine release observed after appropriate antibiotic treatment.
Insights
Pentoxifylline did not prevent the Jarisch-Herxheimer reaction (JHR) or reduce cytokine release in patients treated for Borrelia recurrentis relapsing fever. This study found no benefit of pentoxifylline in managing antibiotic treatment side effects.
Area of Science:
- Infectious Diseases
- Pharmacology
- Immunology
Background:
- The Jarisch-Herxheimer reaction (JHR) is a common, acute febrile reaction occurring after antibiotic treatment for relapsing fever caused by Borrelia recurrentis.
- This reaction is linked to the systemic release of cytokines, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8).
Purpose of the Study:
- To investigate whether pentoxifylline administration prior to antibiotic treatment could prevent or mitigate the JHR and associated cytokine surge in patients with Borrelia recurrentis relapsing fever.
- To assess the impact of pentoxifylline on clinical signs of JHR and circulating cytokine levels.
Main Methods:
- A clinical trial involving 15 patients with confirmed relapsing fever due to Borrelia recurrentis.
- Patients received intravenous pentoxifylline 90 minutes before intramuscular penicillin; 4 patients served as controls without pentoxifylline.
- Clinical parameters (fever, pulse, respiration, blood pressure, white blood cell count) and serum cytokine levels (TNF, IL-6, IL-8) were monitored.
Main Results:
- All patients, regardless of pentoxifylline treatment, experienced JHR to varying degrees.
- Pentoxifylline did not prevent or reduce the severity of fever, changes in vital signs, or alterations in white blood cell counts associated with JHR.
- No significant reduction in circulating levels of TNF, IL-6, or IL-8 was observed in the pentoxifylline group.
- Pentoxifylline did not affect the clearance of Borrelia recurrentis spirochetes.
Conclusions:
- Pentoxifylline administration prior to antibiotic therapy is ineffective in preventing or diminishing the Jarisch-Herxheimer reaction in patients with Borrelia recurrentis relapsing fever.
- The drug failed to suppress the systemic release of key inflammatory cytokines associated with JHR.
- Current evidence suggests pentoxifylline is not a beneficial adjunct for managing JHR in this clinical context.