Regulation of Interleukin 12 p40 and p70 Production by Blood and Alveolar Phagocytes During Severe Sepsis
| Autor: | Frédéric Ethuin, Sylvie Chollet-Martin, Marie-Anne Gougerot-Pocidalo, Laurent Jacob, B Eurin, Charlotte Delarche |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Lipopolysaccharides Male Lipopolysaccharide Phagocyte Neutrophils medicine.medical_treatment Enzyme-Linked Immunosorbent Assay Inflammation Monocytes Pathology and Forensic Medicine Interferon-gamma chemistry.chemical_compound Macrophages Alveolar Humans Protein Isoforms Medicine L-Selectin Molecular Biology Cells Cultured Aged medicine.diagnostic_test business.industry Cell Biology Macrophage Activation Middle Aged Interleukin-12 Systemic Inflammatory Response Syndrome Drug Combinations Bronchoalveolar lavage medicine.anatomical_structure Cytokine chemistry CD18 Antigens Immunology Female medicine.symptom Pulmonary alveolus business Cell activation Bronchoalveolar Lavage Fluid Ex vivo |
| Zdroj: | Laboratory Investigation. 83:1353-1360 |
| ISSN: | 0023-6837 |
| DOI: | 10.1097/01.lab.0000087589.37269.fc |
| Popis: | Paradoxically, the host response to severe sepsis may lead to immunosuppression, thereby favoring nosocomial infections. We examined the role of the two IL-12 isoforms, bioactive IL-12p70 and regulatory IL-12p40, in 16 patients with severe sepsis. We compared the capacity of purified blood and alveolar phagocytes [polymorphonuclear neutrophils (PMN) and monocytes/macrophages] to secrete each isoform. Blood monocytes had normal basal secretions. In contrast, a marked imbalance was observed after ex vivo stimulation by lipopolysaccharide plus IFN-gamma, with significantly lower IL-12p70 production and higher IL-12p40 production. Conversely, stimulated IL-12p40 production by the patients' blood PMN tended to be impaired, as was their cell-surface beta2 integrin and L-selectin expression, known as markers of cell activation. In the patient's bronchoalveolar lavage fluid, the production of both IL-12 isoforms after ex vivo stimulation was significantly lower with alveolar macrophages than with autologous blood monocytes and significantly higher with alveolar PMN than with autologous blood PMN. This sheds new light on the potential role of PMN in local modulation of inflammation, via secretion of the anti-inflammatory IL-12 p40 subunit. The imbalance between the bioactive and regulatory IL-12 isoforms, which is probably designed to control excessive inflammation, may also make septic patients more susceptible to nosocomial infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|