Models in vivo and in vitro for the study of acute and chronic inflammatory activity: A comprehensive review.

Inflammatory conditions are among the principal causes of morbidity worldwide, and their treatment continues to be a challenge, given the restricted availability of effective and safe drugs. Thus, the identification of new compounds with biological activity that can be used for the treatment of inflammatory disorders is an essential field in medical and health research, in order to improve the health and quality of life of patients suffering from these diseases. Evaluation of the anti-inflammatory activity of drugs requires the implementation of models that accurately depict the biochemical and/or physiological responses that characterize human inflammation; for this reason, several in vitro and in vivo models have been developed, providing a platform for discovering novel or repurposed compounds. For this reason, in the present review we have selected twelve commonly used models for the evaluation of the anti-inflammatory effect, and extensively describes the difference between in vivo and in vitro models of inflammation, highlighting their advantages and limitations. On the other hand, the inflammatory mechanisms involved in them, the methods employed for their establishment, and the different parameters assessed to determine the anti-inflammatory activity of a given compound are extensively discussed. We expect to provide a comprehensive guide for the improved selection of a suitable model for the preclinical evaluation of plausible anti-inflammatory agents.

Macrophages morphology and cytokine reeducation by ex situ copper thiol complexes.

OBJECTIVE: To study the reeducation effect of copper thiol complexes on macrophage morphology and cytokine expression. METHODS: The effect of copper thiol complexes was assessed on murine macrophages by the cell morphology observed through optical microscopy, while the expression of cytokines by protein abundance after stimulation. A viability experiment was performed on PMBC to confirm that copper complexes do not affect other cells. RESULTS: The M1 shape was reported after treatment with copper thiol complexes at 1-200 µM, while M2 behavior was documented between 50 and 800 µM. Surprisingly, a thin elongate morphology was observed between 400-800 µM like the M2 shape. The expression of M1 cytokines was noted ranging from 1 to 100 µM, with the highest yield at 1 µM (2243 pg/µL) for the copper-penicillamine complex. M2 production behavior was observed at 1-800 µM, with the highest abundance close to 1150 pg/µL (200-400 µM) was quantified from the copper-cysteine complex. Finally, LCCu complexes did not induce a cytotoxic response on PBMC while exhibiting a high IL-4 and IL-10 production, similar to their gold analogs. CONCLUSIONS: The capacity of copper thiol complexes to reeducate M1 to M2 morphoexpression can be promising for cell protection by using copper thiol penicillamine or immuno-regeneration of tissues when using copper thiol cysteine.