Table 2 Immunomodulatory effects of tetracyclines in preclinical and clinical models of sepsis
From: Immunomodulation by Tetracyclines in the Critically Ill: An Emerging Treatment Option?
Author | Year | Tetracycline | Model | Stimulants or pathogens | Immune response |
|---|---|---|---|---|---|
Colaço et al. [6] | 2021 | Doxycyline | Mouse | E. coli, H1N1 influenza virus, C. albicans, Plasmodium berghei | Liver, lung, kidney injury ↓, mitochondrial protein synthesis ↓; FAO, steroid sensitivity, survival ↑ |
Patel et al. [7] | 2020 | Doxycycline | Mouse | Cecal ligation and puncture | TNF-α, IL-1ß, IL-6, MPO ↓, survival ↑ |
Sun et al. [35] | 2020 | Minocycline | Human THP-1 monocytes | LPS | TNF-α, IL-8, MIP-1α, MIP-1ß ↓, modulated NF-κB-, p38-, ERK1/2-pathways |
Sun et al. [34] | 2015 | Minocycline, tigecycline, doxycycline | Human THP-1 monocytes | LPS | Autophagy ↑ by inhibiting mTOR; TNF-α, IL-8 ↓ |
Nukarinen et al. [48] | 2015 | Doxycycline | RCT | Severe sepsis or septic shock | MMP-8, -9, TIMP-1 ⇔ |
Fredeking et al. [47] | 2015 | Doxycycline | RCT | Dengue virus | IL-6, TNF-α, mortality ↓ |
Bode et al. [45] | 2014 | Doxycycline | Human THP-1 monocytes, PBMCs (ex vivo) | LPS, E. coli | Phagocytosis, IL-1ß, IL-6 ↓, TLR-1, TLR-4, TLR-6 ↓ |
Tai et al. [41] | 2013 | Minocycline | Human THP-1 monocytes | LPS | TNF-α, IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, MIP-1ß, RANTES, eotaxin ↓, IKKα/β phosphorylation inhibited |
Pang et al. [33] | 2012 | Minocycline | Human monocytes (ex vivo) | LPS | TNF-α, IL-1ß, IL-6, COX-2, PGE2 ↓, LOX-1, NF-κB, LITAF, Nur77, PI3K/ Akt-, p38-MAPK pathway ↓ |
Castro et al. [46] | 2011 | Tetracycline, doxycycline | RCT | Dengue virus | IL-6, IL-1ß, TNF-α↓, IL-1ra ↑, TNF-R1 ⇔ |
Maitra et al. [40] | 2005 | CMT-3 | Rat | Cecal ligation and puncture | Liver injury, MMP-9, MMP-2, TGF-ß1, caspase-3 ↓, survival ↑ |
Maitra et al. [38] | 2004 | CMT-3 | Rat | Cecal ligation and puncture | TNF-α↓, p38-, p42/44–MAPK activation inhibited, survival ↑ |
Maitra et al. [39] | 2003 | CMT-3 | Rat | Cecal ligation and puncture | Liver injury, NO, MMP-9 ↓, survival ↑ |
D’Agostino et al. [44] | 2001 | CMTs, | Murine J774 macrophages | LPS | TNF-α, IL-10 ⇔, iNOS, nitrite, NO, IL-12↓, cytotoxity ↑ |
Patel et al. | 1999 | CMTs, minocycline | Murine RAW264.7 cells, human A549 cells | LPS | PGE2, nitrite↓(CMT-3) |
D’Agostino et al. [36] | 1998 | Doxycycline | Mouse, murine macrophages | LPS | NO↓, survival ↑ |
Amin et al. [43] | 1997 | CMTs, doxycycline | Murine macrophages | LPS | iNOS mRNA accumulation and protein expression ↓ |
Milano et al. [37] | 1997 | Tetracycline | Mouse, murine macrophages | LPS | TNF-α, IL-1α, nitrate, iNOS activity ↓, macrophages: NO ↓, TNF-α, IL-1α⇔, survival ↑ |