Burn injuries are unfortunate events with significant physical, psychological, and economic effects on the individual and society. Burn injuries represent a common problem with notable global differences (Keck et al. 2009). According to the literature, burn-related complications are estimated to cause 180 thousand deaths per annum, which renders these injuries an essential public health problem (American Burn Association 2019). Understanding the consequences of burn injuries is very important for the planning of treatment and health services. Burn injuries occur due to various causes including fire burns, scald burns, electrical burns, and chemical burns (AbuBakr et al. 2018). Especially in young children and older adults, scalding is caused by hot liquids or steam (Plancq et al. 2016). Occupational hazards, domestic accidents, and deliberate actions also contribute to the causes of burn injuries.

The severity of burn injuries varies and is usually classified based on the depth and extent of tissue damage. The literature reveals that a significant portion of burn injuries are classified as mild or moderate severity, which includes partial thickness burns (AbuBakr et al. 2018). However, severe burns that also include full-thickness burns may lead to long-term disability and deformation. Burn injuries represent a multifaceted problem that extends beyond visible skin damage. The literature emphasizes that burn injuries may frequently trigger a series of systemic responses, including inflammation, oxidative stress, and changes in immune function (Plancq et al. 2016; AbuBakr et al. 2018). The severity and extent of these responses depend on factors such as burn depth, the total body surface area that has been affected, and the patient’s overall health (Kotzbeck et al. 2019).

Severe burns cause sudden and deep tissue damage at the injury site (Ladhani et al. 2021). The initial effect of a burn injury is localized destruction of skin layers and the tissues underneath. Burn severity, which is measured based on factors such as burn depth and surface area, determines the extent of tissue damage (Laggner et al. 2022). This local injury triggers a series of events that extend beyond the initial site and affect distant organs (Burgess et al. 2022). After a severe burn, an intense inflammatory response is initiated by the mediation of the body’s defense mechanism (Costantini et al. 2022). This response involves the release of various proinflammatory cytokines and mediators such as tumor necrosis factor-alpha (TNF-α) and interleukins (Keck et al. 2009). However, inflammation is a critical aspect of the recovery process; an excessive and uncontrolled inflammatory response may cause secondary damage to organs (AbuBakr et al. 2018). Systemic release of inflammatory mediators may have profound effects on distant organs. This systemic inflammatory response syndrome (SIRS) may lead to increased vascular permeability, tissue edema, and deteriorated organ function (Greenhalgh 2019; Laggner et al. 2022). The lungs, the liver, and the kidneys are particularly susceptible due to their high vascularization and sensitivity to inflammatory changes (Kotzbeck et al. 2019). Among these, the adrenal glands play an essential role in the body’s reaction to stress and the maintenance of homeostasis.

The adrenal glands, located on top of the kidneys, are endocrine organs responsible for the secretion of hormones that help the body manage stress, regulate the metabolism, and maintain the fluid balance (Cappola et al. 2023). These glands are composed of two separate sections: the adrenal cortex and the adrenal medulla. The cortex produces corticosteroids such as cortisol, which have vital importance for specific metabolic processes (Favero et al. 2021). Meanwhile, the medulla secretes catecholamines such as adrenaline and noradrenaline, which play a role in the fight-or-flight response (Cioccari et al. 2020). Severe burns initiate a complex series of physiological reactions, and the adrenal glands are involved in this process (Senel et al. 2010). Burn injuries trigger the release of a large amount of stress hormones as a part of the body’s attempt to cope with the traumatic event (Laggner et al. 2022). The hypothalamic-pituitary-adrenal (HPA) axis, which is an important pathway that regulates stress, is activated and causes an increase in the production of cortisol and other stress hormones (Kotzbeck et al. 2019). In those with severe burns, the adrenal cortex undergoes significant changes (Williams and Herndon 2017). The constant increase in cortisol levels due to burn-induced stress may lead to irregular immune responses. Although cortisol is needed to suppress inflammation, its chronic elevation may suppress immune function, rendering the body more susceptible to infections (Williams and Herndon 2017). Moreover, excessive cortisol secretion may contribute to metabolic disorders, insulin resistance, and impaired wound healing (Ladhani et al. 2021). In some cases, a prolonged stress reaction may induce adrenal failure, decreasing cortisol production (Aissa et al. 2018). The response of the adrenal medulla to severe burns includes an increase in catecholamines, especially adrenalin and noradrenalin (Laggner et al. 2022). These hormones increase the heart rate, blood pressure, and energy mobilization by triggering the fight-or-flight response. Meanwhile, the long-term elevation of catecholamines may lead to high blood pressure and cardiovascular complications such as a higher risk of myocardial ischemia. The damage caused by severe burns to the adrenal glands may lead to broad consequences for the body’s overall homeostasis. Irregular hormonal secretion and prolonged stress response may exacerbate the inflammatory state, endanger immune function, and impair metabolism. Therefore, medical interventions must target these specific problems. Management strategies may involve administering corticosteroid replacement therapy to fix adrenal failure and support immune function. In addition, the control of the stress response via medication and supportive care may help reduce the unfavorable effects of continuous cortisol and catecholamine secretion or prevent the development of adrenal failure.

Severe burns trigger an important systemic reaction characterized by the release of pro-inflammatory cytokines and immune cell activation (Laggner et al. 2022). Interleukin-6 (IL-6) is a key player in this response as it is rapidly released following a burn injury (Keck et al. 2009). The binding of IL-6 to its receptor triggers the activation of JAK enzymes, which in turn phosphorylate signal transducer and activator of transcription 3 (STAT3) (Zhang et al. 2019a, b). When STAT3 is phosphorylated, dimers form and translocate into the nucleus, where they modulate the transcription of the genes involved in tissue repair and cell survival (Li et al. 2022). The activation of the STAT3 pathway and the release of IL-6 in response to severe burns have multifarious effects on the body’s response to trauma, including inflammation, tissue repair, and regeneration, and immunomodulation (Cho et al. 2004; Burgess et al. 2022; Laggner et al. 2022). However, excessive or irregular IL-6/STAT-3 activation may cause systemic inflammatory reactions, impacting distant organs and potentially contributing to complications such as organ dysfunction or multiple organ failure (Zhang et al. 2019b; Jia et al. 2022). Understanding the molecular response mediated by IL-6/STAT-3 in severe burns would be promising for the development of targeted therapeutic interventions. The modulation of this pathway may potentially help manage inflammation, support tissue repair, and prevent the complications related to excessive immune activation.

Anti-inflammatory treatments are essential in the field of burn treatment since burn injuries provoke a substantial inflammatory response (Boldeanu et al. 2020). Commonly used treatments for inflammation include corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and biological medications like cytokine inhibitors (Roshangar et al. 2019). Each of these solutions possesses unique advantages and constraints.

Corticosteroids are commonly employed for their potent anti-inflammatory properties, which aid in diminishing both the localized and systemic inflammatory reaction after burns (Markiewicz-Gospodarek et al. 2022). Nevertheless, the utilization of these substances is a subject of debate because of notable drawbacks, including heightened susceptibility to infection, prolonged recovery of wounds, and the possibility of adrenal suppression when used over an extended period (Perantie and Brown 2002).

NSAIDs are commonly prescribed due to their ability to alleviate inflammation and pain caused by burn injuries (Markiewicz-Gospodarek et al. 2022). While NSAIDs are generally less potent than corticosteroids, they are favored due to their lower incidence of severe adverse effects. The primary issue associated with NSAIDs is their detrimental impact on renal function and gastrointestinal well-being. This can provide a significant challenge, especially for patients with extensive burns who are already susceptible to renal failure and other systemic complications (Bindu et al. 2020). Immunomodulators have the ability to regulate the immune response and, hence, decrease inflammation. However, it is essential to note that prolonged use of certain immunomodulators may have detrimental effects on the immune system (Roshangar et al. 2019; Boldeanu et al. 2020). Despite the availability of different therapeutic techniques for treating inflammation in burn injuries, each approach has notable limitations (Roshangar et al. 2019). The presence of these disadvantages emphasizes the necessity for ongoing investigation into more efficient and less risky methods of reducing inflammation, which could enhance results for individuals with burn injuries.

Hormonal secretion from the adrenal glands is regulated by complex signaling pathways involving numerous receptors, including the alpha-2 adrenergic receptors (Cho et al. 2004; Purnell et al. 2004; Nguyen et al. 2017; Lee 2019). These receptors are found on the surface of a variety of cell types, including those found in the adrenocortical gland (Blandizzi 2007). When activated, alpha-2 adrenergic receptors influence the body’s stress response by modulating hormonal release from the adrenal cortex, protecting homeostasis. Dexmedetomidine, which is a highly selective α2-adrenergic receptor agonist, has emerged as a valuable multifaceted agent in modern anesthesia and intensive care management (Lankadeva et al. 2021). Its unique pharmacological profile, which is characterized by sedative, analgesic, anxiolytic, and sympatholytic properties, sets it apart from conventional sedative agents (Nguyen et al. 2017). Moreover, its effects extend beyond the field of anesthesia and sedation. Its neuroprotective, anti-inflammatory, and organ-protective properties have broadened its use in fields such as neurosurgery and sepsis management (Qiu et al. 2018; Bao et al. 2019). Dexmedetomidine was shown to block the release of IL-6 and other pro-inflammatory cytokines, likely by modulating the sympathetic nervous system and reducing the stress response (Minaei and Haghdoost-Yazdi 2019). Besides, its anti-inflammatory qualities may contribute to the suppression of excessive STAT3 activation, preventing the series of events that may lead to tissue damage (Zhang et al. 2019a). This modulation may potentially protect adrenal gland function by reducing cell damage and inflammation.

Severe burns not only cause visible damage to the skin but also result in complex systemic impairments that may profoundly affect specific organs. Among these, the adrenal glands have an essential role in the body’s response to stress and the maintenance of homeostasis. This study aims to explore the IL-6- and STAT3-mediated effects of dexmedetomidine, an alpha-2 adrenergic agonist, on the adrenal gland by examining the relationship between severe scald burns and adrenal gland damage in rats.