Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor

Nishida, Tomomi; Miyata, Shoji; Itoh, Yoshiki; Mizuki, Nobuhisa; Ohgami, Kazuhiro; Shiratori, Kenji; Ilieva, Iliyana; Ohno, Shigeaki; Taylor, Andrew

doi:10.1016/j.intimp.2004.04.011

Cited by 39 publications

(25 citation statements)

References 27 publications

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“…Therapeutic α-MSH-treatments have been tried in animal models of septic shock, contact dermatitis, rheumatoid arthritis, acute pancreatitis, toxin-induced liver failure, allergic airway inflammation, endotoxin induce uveitis, and experimental autoimmune uveoretinitis (Ceriani et al, 1994;Grabbe et al, 1996;Jahovic et al, 2004;Martin and Lipton, 1990;Nishida et al, 2004;Raap et al, 2003;Shiratori et al, 2004;Taylor et al, 2000;Wang et al, 2004). In addition, two other groups of researchers have attempted to use different forms of gene therapy to see if delivering α-MSH into the immune response of EAE will suppress the onset and subsequent pathology of EAE.…”

Section: Discussionmentioning

confidence: 99%

The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (α-MSH) therapy

Taylor

Kitaichi

2008

Brain, Behavior, and Immunity

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The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) plays an important role in immune privilege by its suppression of inflammation, and its induction of regulatory T cells. This finding led us to test the possibility that we can use α-MSH to suppress autoimmune diseases, and promote re-establishment of immune tolerance to autoantigens. To test this possibility, SJL mice with experimental autoimmune encephalomyelitis (EAE) were injected with α-MSH at the first signs of paralysis. The α-MSH-treated mice in comparison with untreated EAE mice had a profound diminishment in the severity and tempo of EAE. The spleen cells in α-MSH-treated EAE produced TGF-β in response to PLP-antigen stimulation in contrast to untreated mice spleen cells that produced IFN-γ. When the α-MSH-treated EAE mice were reimmunized there was a delay of a week before the second episode of EAE. Although this delay maybe because of the induction of TGF-β-producing spleen cells by the α-MSH-treatment, it was not adequate to suppress IFN-γ-production by PLP-antigen stimulated spleen cells from untreated mice, nor able to suppress the eventual second episode of EAE. Therefore, the injection of α-MSH at the onset of paralysis is extremely effective in diminishing the severity and tempo of EAE, and the subsequent induction of potential PLP-specific Treg cells suggests that an α-MSH therapy could be attempted as part of a therapeutic regiment to impose immunoregulation and immunosuppression on an autoimmune disease of the central nervous system.

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Section: Discussionmentioning

confidence: 99%

The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (α-MSH) therapy

Taylor

Kitaichi

2008

Brain, Behavior, and Immunity

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“…In addition, our research into the immunosuppressive activity of α-MSH and its importance in ocular immune privilege has demonstrated the dynamic contribution of the nervous system to immunoregulation. Further understanding of α-MSH immunomodulating activity will continue to promote the use α-MSH in a therapeutic manner to subdue inflammation and to manipulate immunity to prevent induction of inflammation resulting from specific infections and autoimmune diseases (Casalino-Matsuda et al, 2002;Colombo et al, 2002;Huang et al, 1998;Namba et al, 2002;Nishida et al, 2004;Shiratori et al, 2004). The effects of α-MSH on nitric oxide production by macrophages stimulated by specific TLR.…”

Section: Discussionmentioning

confidence: 99%

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

Taylor

2005

Journal of Neuroimmunology

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Since α-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that α-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with α-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-γ production by Th1 cells. In macrophages treated with α-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of α-MSH in modulating the innate and adaptive immune interface in an inflammatory response.

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“…In a murine model of experimental autoimmune uveitis α-MSH given intravenously significantly suppressed the mean uveitis scores 32. Similarly, intravenous application of α-MSH reduced endotoxin-induced uveitis 33. The anti-inflammatory mechanism of α-MSH in these models appears to be linked to the induction of regulatory T cells since adoptively transferred T cells generated by α-MSH and TGFβ 2 in vitro were also found to suppress experimental autoimmune uveoretinitis 21…”

Section: Anti-inflammatory Effects In Vivomentioning

confidence: 94%

-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs

Luger

Brzoska

2007

Annals of the Rheumatic Diseases

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Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor

Cited by 39 publications

References 27 publications

The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (α-MSH) therapy

The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (α-MSH) therapy

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs

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