The modulatory effects of ketoconazole on cytokine changes induced by selective surgical stress in male rats

• Published in: Comparative clinical pathology 2022-08, Vol.31 (4), p.683-688
• Main Authors: Khamisabadi, Farshad, Pooyanmehr, Mehrdad, Ghashghaei, Ali, Cheraghi, Hadi, Hoseinpour, Fatemeh
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthetics; Antifungal agents; Complications; Corticosterone; Cytokines; Enzyme-linked immunosorbent assay; Glucocorticoids; Hematology; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Immunosuppression; Interleukin 2; Ketoconazole; Medicine; Medicine & Public Health; Midazolam; Oncology; Original Article; Pathology; Pituitary; Postoperative; Propofol; Rodents; Surgery; Sympathetic nervous system; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1618-565X; 1618-5641; 1618-565X
• DOI: 10.1007/s00580-022-03367-9

Surgery and anesthesia cause different metabolic and endocrine responses, including post-operative immunosuppression. The “surgical stress” which occurs before, during, and after an operative procedure causes the immunosuppression. It is the end result of different stimuli such as psychological stress, tissue injury, alterations in circulation, anesthetic agents, and postoperative complications. The hypothalamic–pituitary–adrenal axis, sympathetic nervous system, and cytokines cooperate the stress system. In this study, the levels of serum cytokines including IL-2, TNF-α, and IFN-γ were evaluated following the use of ketoconazole and glucocorticoids (derived from HPA axis) synthesis inhibition. After the adaptation, thirty-six adult male rats were divided equally into three groups as follows: control, K15, and K30. These groups received normal saline, 15 mg/kg bw ketoconazole, and 30 mg/kg bw ketoconazole orally for 3 days every 24 h, respectively. The animals were anesthetized with propofol (100 mg/kg) and midazolam (3 mg/kg); then laparotomy, as a minor surgery, was performed. Four animals from each group were anesthetized by the same anesthetics at T0 (before surgery) and T1 and T2 (24 and 72 h after surgery respectively), blood samples were collected from the heart, and serum cytokines were analyzed by ELISA. Ketoconazole prevented IL-2 suppression and also increased TNF-α levels. This drug could increase IFN-γ levels at 30 mg/kg. Ketoconazole prevents IL-2 suppression by inhibiting corticosterone synthesis and can help to improve the disease. But this drug, by increasing TNF-α, can make various prognoses in different surgeries which may disturb improvement.