A Case of Suspected Adverse Reactions to Sirolimus in the Treatment of Generalized Lymphatic Anomaly

Fujii, Takayuki; Shimono, Ryuichi; Tanaka, Aya; Katami, Hiroto

doi:10.1155/2019/3101357

Cited by 1 publication

(1 citation statement)

References 12 publications

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“…SIR was found to be an effective adjuvant pharmacotherapy for severe refractory IBD in children [9] and adults [10]. However, it has serious adverse effects, such as a depressed immune system and increased susceptibility to infection [11,12]. Therefore, more novel therapeutic targets are urgently needed to control IBD.…”

Section: Introductionmentioning

confidence: 99%

Metformin as an Adjuvant Therapy Attenuates Dextran Sulphate Sodium-induced Acute Colitis in Rats

Magadmi

Aljahdali

Alsawy

et al. 2020

JPRI

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Aims: In numerous cases, patients with inflammatory bowel diseases (IBDs) are refractory to standard treatment. Sirolimus (SIR) and tacrolimus (TAC) are immunosuppressant drugs with encouraging outcomes. However, they have side effects causing limitations in their use. Metformin (MET), which is an antidiabetic drug, has promising anti-inflammatory effects. Thus, this study aimed to validate the effect of the concomitant administration of MET and SIR or TAC in the management of experimentally induced colitis. Study Design: Dextran sulphate (DSS) induced colitis model was used. Methodology: Colitis was induced by administering 5% DSS in water twice daily via oral gavage for 9 days. MET 200 mg/kg alone or in combination with SIR 1 mg/kg or TAC 1 mg/kg was started on day 7 and was continuously administered for 12 days. Then, samples of distal colon tissues were collected for histopathological and immunohistochemistry staining. Then, the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17A levels in tissue homogenates were measured. Results: MET, SIR or TAC significantly attenuated the effect of DSS and the levels of all pro-inflammatory cytokines. Moreover, adding MET reinforces the effect of SIR and TAC. Conclusion: MET had a strong anti-inflammatory effect against DSS-induced colitis. Hence, it could be a promising adjuvant therapy in the management of IBDs. The effect was mediated, in part, by inhibiting NF-κB activation. However, the results of this study must be further validated and translated to clinical implications.

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