1. Introduction:

Acute inflammation, a cornerstone of the body's innate immunity, is a precisely choreographed defense mechanism aimed at countering infections and instigating the healing process after tissue injury. Its pivotal role in sustaining overall health is undeniable. Nonetheless, unchecked or excessive acute inflammation can result in substantial tissue harm and the emergence of chronic inflammatory disorders, posing a severe menace to an individual's well-being. Within this concise review, we embark on a captivating journey into the realm of preclinical acute inflammation models. Here, we systematically examine their defining attributes and their indispensable role in enhancing our comprehension of the convoluted mechanisms dictating inflammation. Preclinical models serve as invaluable tools for researchers, allowing them to replicate and study inflammation in a controlled environment. These models mirror the complex interplay of inflammatory mediators, cells, and pathways observed in human physiology. Through meticulously designed experiments, researchers can assess the efficacy of potential anti-inflammatory agents, unravel the signaling cascades involved in acute inflammation, and gain insights into the dynamic nature of the immune response. Understanding these models is paramount for advancing our knowledge of inflammation's molecular intricacies and the development of novel therapeutic interventions. The information gleaned from these models not only sheds light on acute inflammation but also holds promise for devising strategies to manage chronic inflammatory conditions more effectively, ultimately safeguarding individuals' health and well-being. In the subsequent sections, we delve into specific preclinical models, illuminating their unique features and contributions to our understanding of the multifaceted nature of acute inflammation.

2. Carrageenan:

The Carrageenan-Induced Paw Edema model stands as a widely recognized and reproducible approach for assessing the anti-inflammatory activity of various compounds. Carrageenan, a non-antigenic phlogistic agent derived from certain types of red algae, serves as the catalyst in this model. Upon injection into a paw, it triggers a well-defined and highly predictable acute inflammatory response, characterized by the activation of the complement system and the release of a cascade of inflammatory mediators ^[1]. This cascade primarily involves the activation of the cyclooxygenase pathway, with glucocorticoids and prostaglandin antagonists demonstrating remarkable anti-inflammatory effects ^[2]. One of the most intriguing aspects of the Carrageenan-Induced Paw Edema model is the biphasic nature of the edema response. In the initial phase, acute phase mediators such as serotonin and histamine orchestrate the inflammatory cascade. Subsequently, in the second phase, prostaglandins become the dominant players, illustrating the multifaceted and dynamic nature of acute inflammation ^[3][4]. This model has proven invaluable in deciphering the intricate interplay of mediators and pathways involved in the inflammatory response.

3. Dextran:

The Dextran-Induced Paw Edema model offers unique insights into the mechanisms underlying increased vascular permeability and the activation of critical mediators, including kinins, histamine, and serotonin. In this model, edema formation is primarily osmotic in nature and is characterized by minimal neutrophil infiltration and protein extravasation ^[5][6][7]. Administration of dextran, a complex carbohydrate, leads to the rapid and transient development of edema, underscoring the dynamic nature of acute inflammation and its potential for rapid resolution ^[8][9]. Central to this model is the interaction between histamine and serotonin with their respective receptors, which plays a central role in modulating vascular permeability and edema formation ^[10][11]. The Dextran-Induced Paw Edema model underscores the significance of vasoactive mediators in the orchestration of the inflammatory process and provides a unique perspective on the early phases of acute inflammation.

4. Croton Oil/TPA:

Ear edema induced by croton oil or its irritant principle, 12-O-tetradecanoylphorbol-13-acetate (TPA), serves as a valuable model for assessing the anti-inflammatory activity of a wide array of compounds, including both steroidal and non-steroidal anti-inflammatory drugs. The topical application of croton oil leads to a cascade of inflammatory events, including vasodilation, increased vascular permeability, neutrophil influx, synthesis of eicosanoids, and the release of serotonin and histamine ^[12]. This model's significance lies not only in its relevance to skin inflammation but also in its applicability to both systemic and local anti-inflammatory assessments. The Croton Oil/TPA-Induced Ear Edema model further highlights the intricate interconnections between various inflammatory mediators and pathways. It involves the activation of protein kinase C, mitogen-activated protein kinases (MAPKs), and phospholipase A2, all of which are pivotal players in the orchestration of the inflammatory response ^[13][12]. Through this model, researchers gain profound insights into the complex signaling networks that drive inflammation, facilitating the identification of potential therapeutic targets.

5. Arachidonic Acid:

The Arachidonic Acid-Induced Ear Edema model offers valuable insights into cutaneous inflammation and provides a unique platform for evaluating the potential anti-inflammatory properties of compounds. Arachidonic acid (AA), a key player in this model, undergoes rapid conversion into cyclooxygenase and lipoxygenase products upon topical application. This conversion results in the formation of potent eicosanoids such as prostaglandins, leukotrienes, and thromboxanes, which in turn lead to visible inflammatory symptoms, including erythema, edema, and neutrophil accumulation ^[12]. Local administration of AA also triggers increased expression of interleukin-1β (IL-1β) and mast cell degranulation, further emphasizing the multifaceted nature of acute inflammation and its complex interactions with various cellular and molecular components ^[14]. The anti-inflammatory activity demonstrated by compounds in this model is closely linked to their antihistaminic and antioxidant properties, shedding light on the diverse mechanisms through which potential therapeutics can mitigate inflammation ^[15].

6. Conclusion:

In conclusion, preclinical models of acute inflammation serve as indispensable tools in unraveling the intricate mechanisms that underlie this complex physiological process. Carrageenan-Induced Paw Edema, Dextran-Induced Paw Edema, Croton Oil/TPA-Induced Ear Edema, and Arachidonic Acid-Induced Ear Edema each offer unique and valuable insights into the dynamic and interconnected nature of acute inflammation. These models not only contribute to our fundamental understanding of inflammation but also hold immense potential for guiding the development of therapeutic interventions aimed at mitigating its detrimental effects. Researchers worldwide continue to explore the intricacies of these models and their applications, further advancing our knowledge and offering hope for improved treatments for both acute and chronic inflammatory conditions. The pursuit of this knowledge is essential, as it promises to enhance our ability to combat a wide range of diseases and safeguard the health and well-being of individuals worldwide.