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Recombinant interleukin 2 adjunctive therapy in multidrug-resistant tuberculosis
B Johnson1, L G Bekker, S Ress
1Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021-6399, USA.
Novartis Foundation Symposium
|February 9, 1999
Summary
Low-dose recombinant human interleukin 2 (rhuIL-2) combined with chemotherapy improved treatment outcomes for multidrug-resistant tuberculosis. This immunotherapy enhanced immune responses, reducing bacterial load in most patients.
Area of Science:
- Immunology
- Infectious Diseases
- Molecular Biology
Background:
- Multidrug-resistant tuberculosis (MDR-TB) presents a significant global health challenge, with patients often responding poorly to standard antituberculosis therapy.
- Novel treatment strategies are urgently needed to overcome drug resistance and improve patient outcomes in MDR-TB infections.
Purpose of the Study:
- To evaluate the efficacy of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with chemotherapy for MDR-TB.
- To investigate the immunomodulatory effects of rhuIL-2 therapy in MDR-TB patients.
Main Methods:
- Patients with MDR-TB received daily rhuIL-2 (low dose) for 30 days alongside standard chemotherapy.
- Immune system activation was assessed by monitoring changes in blood cell populations (CD25+, CD56+) and gene expression (gamma-interferon, IL-2 mRNA) at a delayed-type hypersensitivity (DTH) skin test site.
- Differential display reverse transcriptase PCR was used to identify genes differentially regulated by rhuIL-2 at the DTH site.
Main Results:
- Approximately 60% of MDR-TB patients treated with rhuIL-2 and chemotherapy showed reduced or cleared sputum acid-fast bacilli.
- Daily rhuIL-2 administration led to increased CD25+ and CD56+ immune cells in the blood.
- rhuIL-2 therapy upregulated gamma-interferon and IL-2 mRNA expression at the DTH response site.
- Several genes involved in cellular functions, including endocytic pathways and respiratory enzymes, were found to be differentially expressed during rhuIL-2 treatment.
Conclusions:
- Combination therapy with low-dose rhuIL-2 demonstrates potential as an effective treatment modality for multidrug-resistant tuberculosis.
- rhuIL-2 enhances immune activation, contributing to antimycobacterial responses.
- Further research is ongoing to elucidate the precise roles of differentially expressed genes in rhuIL-2-mediated immune modulation and antimycobacterial activity.