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

Inflammation is a local response of tissue to injury, trauma, infection, or irritants, initially mediated by the innate immune system; it is the defense reaction aimed at eliminating or limiting the spread of injurious stimuli [3]. The acute phase of inflammation is characterized by swelling, pain, redness, and heat due to the underlying immune process involving blood flow increase, vascular permeability, fluid accumulation, leukocyte infiltration, nerve fiber sensitization, and inflammatory mediators' production [6]. On the other hand, the chronic phase evolves when inflammation is prolonged, and the overall response is dysregulated, leading to poor homeostasis and paving the way for the development of pathologic conditions such as autoimmunity, arthritis, and cancer [31](Table 1).

Inflammatory diseases are among the major causes of morbidity worldwide, and their treatment continues to be a challenge given the lack of effectiveness and safeness of available drugs [69]. Many conventional drugs widely employed to keep inflammatory diseases in checks, such as glucocorticoids and non-steroidal anti-inflammatory drugs, come along with adverse side-effects and complications: vomiting, nausea, diarrhea, gastric ulceration, and kidney problems – especially aggravated with long-term use[60]. Due to these limitations, identifying novel compounds with biological activity against the development of inflammatory processes is a major need in modern medicine. According to the World Health Organization (WHO), throughout the world, traditional medicine is either the pillar of healthcare delivery or acts as a complement to it, and compounds of proven efficacy and safety contribute to ensuring that all individuals have access to quality and affordable care. Growing interest and research in plant-derived molecules (called phytoconstituents) based on their employment in traditional medicine have proven their potential to be a significant source of drug candidates against various diseases, especially chronic ailments [82].

Diverse in vivo and in vitro models have been developed to screen and evaluate drugs with possible anti-inflammatory and antinociceptive properties, allowing the development and discovery of novel or repurposed compounds derived from traditional and conventional medicine. Selecting a suitable model for preclinical evaluation is necessary to demonstrate the effectiveness and elucidate the mechanisms of action of agents under assessment, identifying a drug with real potential to render therapeutic effects on humans. Although there are previous works reviewing inflammation models, most focus on animal models, leaving in vitro models out of the picture. This review aims to comprehensively describe the different inflammation models in vivo and in vitro, the inflammatory mechanisms involved, and the standard methods used to establish and evaluate compounds with anti-inflammatory activity.

To evaluate the potential anti-inflammatory effect of new drugs and plant extracts, it has been used different experimental in vivo models for acute and chronic inflammation. In this section, we have summarized the most used animal models which are: 1. Carrageenan-induced inflammation assay, 2. Carrageenan-Induced Peritonitis, 3. TPA-Induced Ear Edema, 4. Xylene-Induced Ear Edema, 5. Acetic Acid-Induced Vascular Permeability, 6. Formalin-Induced Paw Edema, Subcutaneous Air Pouch, 7. Complete Freund’s Adjuvant (CFA)-Induced Arthritis, 8. Complete Freund’s Adjuvant (CFA)-Induced Arthritis, 9. Cotton Pellet-Induced Granuloma (Table 2).

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