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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antigens, CD, Collagenases, Cytokines, Fetus, Humans, Interleukin-12, Interleukin-18, Interleukin-18 Receptor alpha Subunit, Intestinal Mucosa, Intestines, Matrix Metalloproteinase 3, Matrix Metalloproteinase Inhibitors, Organ Culture Techniques, Protein Isoforms, Proteins, Receptors, Interleukin, Receptors, Interleukin-12, Receptors, Interleukin-18, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Fusion Proteins, Th1 Cells.
user
Does enhancing Lamina propria Th1 cell responses with interleukin 12 produce severe tissue injury? Context: Interleukin (IL)-12 is believed to modulate local T-cell response in human colitis. A direct functional relationship between IL-12 and tissue injury in human intestine has not been reported. The aim of this study was to examine changes that take place in explant cultures of human fetal gut after stimulation of T cells with anti-CD3 in the presence of exogenous IL-12/IL-18. T cells in explants of fetal gut were activated with anti-CD3 antibody and/or IL-12 or IL-18. Mucosal pathology was determined by immunohistochemistry. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay were used to determine cytokine synthesis, and the production of matrix metalloproteinases was analyzed by RT-PCR and Western blotting. Activation of T cells in explants with anti-CD3 antibody elicited very little interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and no tissue injury. Addition of graded doses of IL-12 with anti-CD3 resulted in a significant increase in both IFN-gamma and TNF-alpha. This change was associated with a massive increase in stromelysin-1 expression and severe tissue injury, which was inhibitable by a stromelysin-1 inhibitor. Costimulation of explants with anti-CD3 and IL-18 induced only IFN-gamma and no tissue injury.
assistant
IL-12 can convert a physiological T-cell signal into a strong signal with the downstream effect of elevating tissue stromelysin-1 concentration and mucosal degradation. Final Decision: yes