Natural Adrenocorticotropic Hormone (ACTH) Relieves Acute Inflammation in Gout Patients by Changing the Function of Macrophages

Abstract

Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU)-induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. However, gout patients manifest other complications, such as hypertension, diabetes, chronic kidney disease, and hormone intolerance, which limit efficacy of some of these first-line drugs. Therefore, this study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. We analyzed the variations in VAS pain scores of five patients, knowing the time of action and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in the mouse model was evaluated by studies in vivo. In vitro studies, we evaluated the effect of natural ACTH on macrophages and revealed different functions of ACTH and dexamethasone on macrophages in the transcriptional level. In patients with acute gout, natural ACTH can quickly alleviate pain and does not affect the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exerts different effects on the transcription of some related genes. Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone at the transcriptional level.

Understanding the Immune System’s Intricate Balance: Activation, Tolerance, and Self-Protection

“…ACTH's influence extends further, inhibiting Th17-like innate immune reactions, a subtle modulation akin to a skilled composer introducing unexpected harmonic progressions [53][54][55][56]. This delicate interplay between ACTH and glucocorticosteroids, a Yin-Yang regulation of endocrinemediated immune control, ensures that the body's defensive forces remain poised, neither overreacting to innocuous threats nor succumbing to unchecked autoimmunity.…”

Fda-Approved Indications of Adrenocorticotropic Hormone (Acth) as a Drug: Does It Have a Place in Disease Management Today?

“…In this light, macrophages could be regarded as potent orchestrators of gout inflammation. Xu et al [91] studied how ACTH application could affect macrophage function in a mouse model and in 5 patients with gout. MSU crystals were injected in the right footpad of mice, inflicting arthritis.…”

“…Nguyen et al [16], Sharon et al [17] and Nelson et al [18] eye uveitis Bryan et al [20] eye optic neuritis Wirta et al [21] eye keratitis Anesi et al [22] eye retinal vasculitis Cusick et al [38], Kaplan et al [39], [40], Hunter et al [41] nervous system multiple sclerosis Chugani et al [44], Knupp et al [45], O'Callaghan et al [47], Yin et al [50] pediatrics infantile spasms Gills et al [55], Fleischmann et al [57] musculoskeletal rheumatoid arthritis Furie et al [66,67], Askanase et al [68,69] musculoskeletal sle Aggarwal et al [74] musculoskeletal inflammatory myopathy Baughman et al [75], Chopra et al [76], Rahaghi et al [77] musculoskeletal sarcoidosis Daoussis et al [85], [86], Xu et al [91] musculoskeletal gout…”