Can Lyme disease cause a significant elevation in Interleukin-18 (IL-18) levels?

From the Guidelines

Lyme disease can potentially cause a significant increase in interleukin-18 (IL-18) levels as part of the body's immune response to the infection. The bacterium Borrelia burgdorferi, which causes Lyme disease, triggers an immune response that includes the production of various inflammatory cytokines, including IL-18. When the immune system detects the Borrelia infection, it activates inflammasomes, particularly the NLRP3 inflammasome, which processes pro-IL-18 into its active form 1. This activation can lead to markedly elevated IL-18 levels as part of the body's attempt to combat the infection. The increase in IL-18 contributes to the inflammatory response seen in Lyme disease and may be associated with some of the symptoms patients experience, such as fever, fatigue, and joint pain.

Some key points to consider in the management of Lyme disease include:

• The use of antibiotic treatment, such as doxycycline, to combat the infection 1
• The importance of confirming the diagnosis through standard Lyme testing (ELISA followed by Western blot)
• The potential need for hospital admission with continuous ECG monitoring in patients with severe cardiac complications of Lyme disease, including those with significant PR prolongation, other arrhythmias, or clinical manifestations of myopericarditis 1
• The recommendation for oral regimens, such as doxycycline, for the treatment of early neurologic disease, including meningitis or radiculopathy, and for the treatment of late disease, including arthritis without neurologic disease 1

In terms of treatment, doxycycline 100mg twice daily for 10-21 days is a commonly recommended regimen for the treatment of Lyme disease, depending on disease manifestations. It is essential to note that the treatment duration and regimen may vary depending on the specific clinical manifestation of the disease and the patient's response to treatment.

Overall, the management of Lyme disease requires a comprehensive approach that takes into account the patient's clinical presentation, laboratory results, and response to treatment. By prioritizing the patient's morbidity, mortality, and quality of life, healthcare providers can provide effective care and improve outcomes for patients with Lyme disease.

From the Research

Interleukin-18 (IL-18) Levels in Lyme Disease

• The study 2 found that serum levels of IL-18 were significantly higher in patients with Lyme arthritis compared to the control group.
• The same study 2 also found that after antibiotic treatment, the concentrations of IL-18 decreased significantly, but still remained higher than in the control group.
• Another study 3 did not specifically investigate IL-18 levels in Lyme disease, but it did identify several proteins with altered serum levels in patients with early Lyme disease.
• A review article 4 discussed the role of IL-18 in immunity, inflammation, and autoimmunity, but did not specifically address its relationship with Lyme disease.
• However, a review article 5 mentioned that chronic excess of serum IL-18 is associated with various immune-mediated inflammatory diseases, but it did not specifically discuss Lyme disease.
• None of the studies directly investigated the effect of Lyme disease on IL-18 levels, except for the study 2 which found a significant elevation in IL-18 levels in patients with Lyme arthritis.

Acute-Phase Response in Lyme Disease

• A study 6 found that C-reactive protein (CRP) and serum amyloid A (SAA) levels were significantly elevated in early localized and early disseminated Lyme disease, but not in the later stages of active infection.
• The same study 6 also found that CRP levels were significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.
• The study 2 found that CRP levels were only elevated in 6 out of 20 patients with Lyme arthritis, and in 5 of them it returned to baseline after treatment.

IL-18 and Lyme Disease

• Based on the available evidence, it appears that Lyme disease can cause a significant elevation in IL-18 levels, at least in patients with Lyme arthritis 2.
• However, more research is needed to fully understand the relationship between IL-18 and Lyme disease, and to determine whether IL-18 can be used as a biomarker for diagnosis or treatment monitoring.