Preventive Immunomodulatory Effects of Doxycycline and Hyperbaric Oxygen Therapy on Serum Tumor Necrosis Factor-α and Interleukin-6 Levels in a Rat Model of Malaria.
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BACKGROUND: Malaria remains a major global health problem causing morbidity and mortality. Although doxycycline is widely used as an effective malaria chemoprophylactic agent, its use is limited in certain populations (doxycycline should not be given to children under 8 years of age and pregnant women). These limitations, together with the growing challenge of antimalarial drug resistance, necessitate the exploration of adjunctive and alternative prophylactic strategies. Hyperbaric oxygen therapy (HBOT), which involves inhalation of 100% oxygen under increased atmospheric pressure, has demonstrated immunomodulatory and anti-inflammatory effects in various infectious diseases. OBJECTIVE: This study is aimed at evaluating the preventive immunomodulatory effects of doxycycline and HBOT, alone or in combination, on the serum levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a Plasmodium berghei rat model. METHODS: An in vivo experimental study was conducted using 24 female BALB/c mice (7-10 weeks old), randomly assigned into four groups: control group (CG), doxycycline group (DG), hyperbaric oxygen therapy group (HG), and combined doxycycline-hyperbaric oxygen therapy group (DHG). All groups were infected with P. berghei ANKA. Serum TNF-α and IL-6 levels were measured and compared among the groups. RESULTS: Significant differences in TNF-α (p = 0.012), IL-6 (p = 0.010), and parasitemia (p = 0.001) were observed among the four groups. TNF-α levels were significantly lower in DG, HG, and DHG than in CG (p = 0.037, p = 0.004, and p = 0.004, respectively), whereas no significant differences were observed among the treatment groups. IL-6 was significantly lower in HG and DHG than in CG (both p = 0.004), whereas the difference between DG and CG was not statistically significant (p = 0.150). All treatment groups showed significantly lower parasitemia than CG (all p = 0.001). HBOT and DHG also showed lower parasitemia than DG (p = 0.020 and p = 0.006, respectively), whereas no significant difference was observed between HG and DHG (p = 0.952). CONCLUSION: Both doxycycline and HBOT exert immunomodulatory effects by reducing TNF-α and IL-6 levels in experimental malaria. The present findings suggest that doxycycline and HBOT may modulate systemic inflammatory responses during experimental malaria. Combination of doxycycline and HBOT shows a favorable anti-inflammatory profile against malaria-associated inflammation.