The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor

Abstract

A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γ c). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γ c subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2-and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γ c receptor-dependent cytokines, i.e. IL

The contribution of probiotics for the double-edge effect of cefazolin on postoperative neurocognitive disorders by rebalancing the gut microbiota

“…It has been demonstrated that minocycline mitigates isoflurane-induced cognitive impairment in aged rats ( Li et al, 2013 ). According to reports, cefazolin is a common gamma-chain cytokine inhibitor with anti-inflammatory properties ( Zyzynska-Granica et al, 2020 ). Our research group has recently demonstrated that cefazolin can inhibit lipopolysaccharide-induced inflammation ( Liang et al, 2018 ).…”

Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses

“…Interleukin-17 is a key cytokine that links T-cell activation to neutrophil mobilization and activation, and IL-17 mediates innate immunity to pathogens or contribute to the pathogenesis of inflammatory disease ( 57 ). In previous literature, cefazolin, a first-generation cephalosporin antibiotic, was shown to interact with IL-15-dependent TNF-α and IL-17 synthesis ( 58 ). Cefazolin reduced production of IL-17, among other various cytokines ( 58 ).…”

Integrating heterogeneous data to facilitate COVID-19 drug repurposing

“…However, recent studies have shown in-silico and in-vitro evidence that cefazolin can bind to some cytokine receptors (including the IL2 receptor), and therefore inhibits the proliferation and differentiation of immune cells, and the production of cytokines. [18] , [19] This could help to mitigate the effects of the excessive immune response that SARS-CoV-2 induces in some patients. In addition, cefazolin could treat secondary bacterial pneumonia induced by COVID-19.…”