| Autor: |
Schäufele, Tim J., Kolbinger, Anja, Friedel, Joschua, Gurke, Robert, Geisslinger, Gerd, Weigert, Andreas, Pierre, Sandra, Scholich, Klaus |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Apr2024, Vol. 181 Issue 7, p1051-1067, 17p |
| Abstrakt: |
Background and Purpose: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the most widely prescribed drugs in the world due to their analgesic, antipyretic and anti‐inflammatory effects. However, NSAIDs inhibit prostanoid synthesis, interfering with their pro‐inflammatory and anti‐inflammatory functions and potentially prolonging acute inflammation. Experimental Approach: We used high‐content immunohistochemistry to define the impact of meloxicam treatment on spatially separated pro‐inflammatory and anti‐inflammatory processes during innate inflammation in mice induced by zymosan. This allowed us to determine the effect of meloxicam treatment on the organization of pro‐inflammatory and anti‐inflammatory microenvironments, thereby identifying relevant changes in immune cell localization, recruitment and activation. Key Results: Meloxicam treatment reduced zymosan‐induced thermal hypersensitivity at early time points but delayed its resolution. High‐content immunohistochemistry revealed that the pro‐inflammatory area was smaller after treatment, diminishing neutrophil recruitment, M1‐like macrophage polarization, and especially phagocytosis by neutrophils and macrophages. The polarization of macrophages towards the M2‐like anti‐inflammatory phenotype was unaffected, and the number of anti‐inflammatory eosinophils actually increased. Conclusion and Implications: High‐content immunohistochemistry was able to identify relevant meloxicam‐mediated effects on inflammatory processes based on alterations in the regional structure of inflammation sites. Meloxicam delayed the clearance of pathogens by inhibiting pro‐inflammatory processes, causing prolonged inflammation. Our data suggest that the prescription of NSAIDs as a treatment during an acute pathogen‐driven inflammation should be reconsidered in patients with compromised immune systems. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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