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Cellular immunity in tuberculosis involves activated macrophages releasing tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Tuberculin-positive individuals, including those with tuberculosis, show higher TNF-alpha production from macrophages.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Context:
- Cellular immune responses are crucial in managing tuberculous infections.
- Activated macrophages accumulate at infection sites, phagocytosing bacteria but also causing tissue damage through enzyme and cytokine release.
- Understanding macrophage-mediated necrosis is key to tuberculosis pathogenesis.
Purpose:
- To investigate the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by human monocytes/macrophages (M phi) in response to stimulation.
- To compare cytokine production in individuals with varying tuberculin reactivity and tuberculosis status.
Summary:
- Human monocytes/macrophages were isolated from healthy tuberculin-negative, healthy tuberculin-positive, and tuberculosis patients.
- Cells were stimulated with lipopolysaccharide (LPS) or muramyl dipeptide (MDP), and TNF-alpha and IL-6 levels in supernatants were measured.
- Monocytes/macrophages from tuberculin-positive individuals (with or without TB) exhibited higher TNF-alpha production compared to tuberculin-negative individuals.
Impact:
- Findings suggest a link between cellular immune status, macrophage activation, and cytokine profiles in tuberculosis.
- Macrophage-derived TNF-alpha may play a significant role in the inflammatory and necrotic processes observed in tuberculosis.
- This research contributes to understanding the immunological mechanisms underlying tissue damage in tuberculosis.
Abstract:
Cellular immune reaction plays an important role in tuberculous infection. When the host develops cellular immunity, a large number of activated macrophages (M phi) are accumulated in the tuberculous focus by the chemotactic effect of lymphokine, and these M phi lively phagocytize and suppress the multiplication of tubercle bacilli. On the other hand, many M phi are killed during the process of phagocytosis, releasing a large amount of lysosomal enzymes and cytotoxic substances (TNF etc.), possibly causing the tissue damage: caseous necrosis, softening and liquefaction followed by cavity formation. To clarify the process of necrosis in detail, production of TNF-alpha and IL-6 from human M phi was observed. Monocyte/M phi were separated from the peripheral blood of healthy persons, each group with positive or negative tuberculin reaction and tuberculous patients, using a commonly used method. The monocyte/M phi were stimulated in a culture with lipopolysaccharide (LPS) or muramyl dipeptide (MDP) and amount of TNF-alpha and IL-6 in the culture supernatants were estimated. TNF-alpha activity was determined by measuring the lysis of the target cell (mouse L929 cell), and IL-6 by measuring the 3H-thymidine incorporation into IL-6 dependent mouse plasma cell hybridoma, MH60-BSF2, in the presence of TNF-alpha or IL-6, respectively. The results showed that the monocyte/M phi from the tuberculin positive persons, with or without tuberculosis revealed a higher TNF-alpha production activity than those from tuberculin negative healthy cases using either MDP or LPS stimulation. The monocyte/M phi from tuberculous patients produced more TNF-alpha with MDP stimulation than with LPS.(ABSTRACT TRUNCATED AT 250 WORDS)