[A putative immunotherapy with biological response modifiers (BRM) against intractable pulmonary tuberculosis]

Area of Science:

• Immunology
• Infectious Diseases
• Cytokine Biology

Background:

• Tuberculosis (TB) is a growing concern in Japan, especially among aging and immunocompromised populations.
• Cell-mediated immunity, particularly the Th1-Th2 cytokine balance, is crucial for controlling Mycobacterium tuberculosis infections.
• Interleukin-12 (IL-12) and Interleukin-18 (IL-18) are key cytokines influencing Th1 cell differentiation and function.

Observation:

• Steroid treatment and Acquired Immunodeficiency Syndrome (AIDS) are significant host factors impacting TB outcomes.
• Murine models demonstrated that exacerbated TB infections correlate with decreased interferon-gamma (IFN-γ) production under these conditions.
• The study explored the influence of various host factors on the Th1-Th2 cytokine balance and TB infection outcomes.

Findings:

• Therapeutic effects of Th1-type cytokines were observed in a murine model of fatal M. tuberculosis infection.
• A combined therapy of anti-tuberculosis agents and IFN-γ showed promise in treating intractable multidrug-resistant pulmonary TB in a patient with diabetes.
• While IL-12 is under investigation for cancer therapy, its clinical use in infectious diseases is pending, and IL-18 is not yet in clinical trials.

Implications:

• Restoring Th1-type cytokine balance, particularly IFN-γ, could be a viable therapeutic strategy for intractable TB.
• Immunotherapy with Th1 cytokines may offer clinical benefits for difficult-to-treat tuberculosis cases.
• Further research into IL-12 and IL-18 may lead to novel treatments for infectious diseases, including TB.