Macrolides | AZM | Human (RCT) | Nasal and endotracheal samples | RSV | MMP-9, IL-1, IL-10, TNF-α (endotracheal) ↓, nasal ⇔ | NA | NA | NA | NA | Kong et al. [71] |
AZM | Mouse | Macrophages (J774) | LPS | M2 macrophages (via inhibition of NF-κB STAT1 pathways) ↓ | NA | NA | NA | NA | Haydar et al. [33] |
CAM | Mouse | BALF, lung tissue, serum | H1N1 influenza virus, S. pneumoniae i.n. | IFN-γ ↓, IL-10 ↑ CD11b+Gr-1+ MDSC-like cells (via STAT3 pathway) ↑ | ↓ | ND | ND | ↑ | Namkoong et al. [39] |
AZM | Mouse | BALF, lung tissue | RSV i.n. | IL-5, IL-6, IFN-γ ↓ | ⇔ | ND | ↓ | ↑ | Mosquera et al. [41] |
AZM | Mouse | Lung tissue | H1N1 influenza virus i.n. | IL-6, TNF-α ⇔ | ND | ND | ND | ⇔ | Fage et al. [64] |
AZM | Mouse | BALF, lung tissue, blood plasma | Radiation | IL-1β, IL-6, TNF-α, TGF-β1, α-SMA, COL1A1 ↓, oxidative damage (lipid peroxidation) ↓ | ND | ND | ↓ | ND | Tang et al. [40] |
AZM | Mouse | BALF, lung tissue | P. aeruginosa i.t. | Caspase-1 activation ↓, IL-1β cleavage ↓ IL-1β, IL-18 ↓ | ↓ | ↓ | ↓ | ND | Fan et al. [30] |
AZM | Human (cohort study) | Blood plasma, PBMCs | H3N2 influenza virus | IL-6, CXCL8, IL-17, CXCL9, sTNFR-1, IL-18, IFN-γ, IP-10 ↓ | ND | ND | ND | ND | Lee et al. [42] |
AZM | Human (cohort study) | Blood plasma, BALF | Community-acquired pneumonia | IL-6, TNF-α (plasma)↓, IL-8, lL-10 (BALF)↓ | ND | ND | ND | ND | Lorenzo et al. [70] |
CSY0073, AZM | Mouse | BALF, lung tissue, alveolar macrophages, BEC | LPS i.n. | TNF-α, CXCL1, CXCL2, IL-6, IL-1β ↓ | ↓ | ND | ND | ND | Balloy et al. [144] |
AZM | Mouse | BALF | LPS i.t. | NF-κB, TNF-α, G-CSF, IL-6, IL-9, MCP-1↓ | ↓ | ND | ND | ND | Stellari et al. [35] |
CAM | Mouse | BALF, lung tissue | Ventilation | NF-κB, E-selectin ↓ MMP-2, MMP-9⇔ | ↓ | ⇔ | ↓ | ND | Amado-Rodríguez et al. [36] |
AZM | Mouse | BALF, lung tissue | A. baumanii i.b. | IL-1β, IL-6, MIP-2, macrophages, lymphocytes ↓ | ↓ | ND | ↓ | ↑ | Yamada et al. [48] |
CAM | Human (in vitro) | Alveolar epithelial cells (A549) | RSV, S. pneumoniae | IL-6, IL-8, CCL5/Rantes ↓ PAF receptor expression ↓ | NA | NA | NA | NA | Yokota et al. [51] |
CAM | Human (RCT) | Monocytes, neutrophils | Ventilator-associated pneumonia | IL-6, monocyte apoptosis, CD86, TREM-1↑, TNF-α ↓, restored TNF-α/IL-10 ratio | ND | ND | ND | ND | Spyridaki et al. [8] |
AZM | Mouse | BALF, lung tissue, macrophages (J774) | LPS i.n. | IL-1β ↓ by inhibition of AP-1 activation, NF-κB, ERK-1 and -2 ⇔ | ↓ | ND | ↓ | ND | Bosnar et al. [31] |
AZM | Mouse | BALF, lung tissue | P. aeruginosa i.t. | TNF-α, IL-6, CCL2↓, IFN- γ, IL-10, IL-12p70 ⇔, M2 macrophages, arginase1, mannose receptor, CD11b+Gr-1+ MDSC-like cells ↑ | ⇔ | ND | ND | ⇔ | Feola et al. [38] |
CAM | Mouse | BALF, lung tissue | H. influenzae i.t. | IL-1β, MIP-2 ↓ | ↓ | ND | ↓ | ND | Nakamura et al. [47] |
CAM | Human (in vitro) | Tracheal epithelial cells | H3N2 influenza virus | IL-1β, IL-6, IL-8, NF-κB (p50, p65) ↓ | NA | NA | NA | NA | Yamaya et al. [34] |
AZM, CAM | Mouse | BALF, lung tissue, macrophages (J774) | LPS i.n. | MCP-1/CCL2, GM-CSF, IL-1β, TNF-α, E-selectin, MPO concentration↓ CXCL1, CXCL2 ⇔ | ↓ | ND | ND | ND | Bosnar et al. [43] |
CAM | Mouse | BALF, lung tissue, alveolar macrophages | K. pneumoniae i.n. | Oxidative damage (NO, MDA, MPO) ↓, macrophage phagocytic activity ↑ | ↓ | ND | ↓ | ND | Kumar et al. [44] |
AZM | Mouse | Macrophages (J774) | LPS | M2 macrophages ↑ (IL-10, IL-23, mannose receptor, CD23 ↑; IL-6, IL-12, CCR7, iNOS ↓) | NA | NA | NA | NA | Murphy et al. [56] |
AZM | Human (ex vivo) | PBEC | LPS | IL-8, GM-CSF ↓, VEGF ⇔ | NA | NA | NA | NA | Murphy et al. [49] |
EM703 | Mouse | BALF, lung tissue | Bleomycin i.v. | TGF-β, macrophages, fibroblasts ↓ | ↓ | ND | ↓ | ND | Li et al. [62] |
AZM | Mouse | Lung tissue | P. aeruginosa i.t. | KC/CXCL1, TNF-α ↓, inhibition of ERK-1 and -2 activation | ↓ | ND | ND | ND | Tsai et al. [46] |
CAM | Mouse | BALF, lung tissue | M. pneumoniae i.n. | IFN-γ, TNF-α, IL-6, KC/CXCL1, MIP-1α, MCP-1 ↓ | ND | ND | ↓ | ND | Hardy et al. [50] |
CAM, RXM, AZM, JM | Mouse | BALF, lung tissue | Bleomycin i.t. | KC/CXCL1 ↓ (RXM, CAM), apoptosis of bronchial and alveolar epithelial cells ↓ (RXM>CAM>AZM) | ↓ (RXM> CAM>AZM), JM ⇔ | ↓ (RXM> CAM>AZM), JM ⇔ | ↓ (RXM> CAM>AZM), JM ⇔ | ND | Kawashima et al. [45] |
ERM | Mouse | BALF, serum, macrophages (RAW 264.7) | H2N2 influenza virus nebulisation | IFN-γ, NO metabolites (nitrite, nitrate) ↓, macrophages, lymphocytes ↓ | ⇔ | ND | ND | ↑ | Sato et al. [63] |
Ketolides | TEL | Mouse | BALF, macrophages (RAW 264.7), epithelial cells (MLE-12) | LPS nebulisation | Nitrite, MIP-2, TNF-α ↓ | ↓ | ↓ | ND | ND | Leiva et al [75] |
Tetracyclines | TET | Mouse, human (ex vivo) | BALF, BMDM; alveolar leucocytes | LPS, H1N1 influenza virus i.t. (mouse); viral, bacterial and non-pulmonary ARDS (human) | IL-1β, IL-18, caspase-1 activation ↓ | ↓ | ND | ↓ | ↓ | Peukert et al. [9] |
DOX | Mouse | Lung tissue, blood plasma | Caecal ligation and puncture | TNF-α, IL-1β, IL-6, MPO ↓ | ND | ND | ND | ↑ | Patel et al [84] |
DOX | Mouse | BALF, lung tissue, serum | Paraquat i.t. | MMP-9, MPO ↓ | ↓ | ND | ↓ | ND | Zhang et al. [147] |
DOX | Rat | BALF, lung tissue, blood plasma | Cardiopulmonary bypass | TNF-α, IL-1β, MMP-9 ↓ | ND | ↓ | ↓ | ND | Wang et al. [85] |
DOX | Dog | BALF, lung tissue, blood plasma | Cardiopulmonary bypass | MMP-9, MPO ↓ | ↓ | ↓ | ↓ | ND | Zhang et al. [82] |
CMT-3 | Pig | BALF, lung tissue, blood plasma | Ischaemia by clamping of SMA, placement of faecal clot in peritoneum | TNF-α, IL-1β, Il-6, IL-8, IL-10 ↓, MMP-2, -9, NE ⇔ | ND | ⇔ | ↓ | ⇔ | Roy et al. [86] |
DOX | Mouse | BALF, lung tissue | H3N2 influenza virus i.n. | MMP-2, MMP-9, T1-α, thrombomodulin ↓ | ↓ | ↓ | ↓ | ND | Ng et al. [91] |
DOX | Mouse | BALF, lung tissue | LPS i.t. | Syndecan-1 (substrate of MMP-7) ↓ | ↓ | ⇔ | ↓ | ND | Moon et al. [79] |
CMT-3 | Sheep | Lung tissue, blood plasma | Third-degree burn, smoke inhalation, barotrauma injuries | MMP-2 ↓, MMP-9 ⇔ | ND | ND | ↓ | ↑ | Zhou et al. [94] |
DOX | Rat | Lung tissue | Acute pancreatitis (intraductal glycodesoxycholic acid, cerulein i.v.) | MMP-9 ↓ | ↓ | ↓ | ↓ | ND | Sochor et al. [80] |
DOX | Mouse | BALF, lung tissue | LPS or S. pneumoniae i.t. | MMP-2, -9 ↓ | ↓ | ND | ↓ | ↑ | Fujita et al. [81] |
CMT-3 | Rat | BALF, lung tissue | Ventilation | MMP-9, MPO ↓ | ↓ | ↓ | ↓ | ND | Kim et al. [88] |
CMT-3 | Pig | BALF, lung tissue, serum, blood plasma | Ischaemia by clamping of SMA Placement of faecal clot in peritoneum | IL-6, IL-8, IL-10, NE ↓, IL-1, MMP-2, -9 ⇔ | ⇔ | ND | ↓ | ↑ | Steinberg et al. [87] |
CMT-3 | Rat | BALF, lung tissue, serum | Caecal ligation and puncture | MMP-2, MMP-9 ↓ | ND | ↓ | ↓ | ↑ | Steinberg et al. [78] |
CMT-3 | Pig | BALF, lung tissue | LPS i.v. | MMP-2, MMP-9 ↓ | ↓ | ↓ | ↓ | ND | Carney et al. [93] |
CMT-3 | Pig | Lung tissue | Cardiopulmonary bypass, LPS i.v. | ND | ↓ | ND | ND | ND | McCann et al. [92] |
CMT-3 | Pig | BALF, lung tissue | Cardiopulmonary bypass, LPS i.v. | MMP-2, NE ↓ | ↓ | ↓ | ↓ | ND | Carney et al. [83] |
Oxazolidinones | LZD | Human (ex vivo) | Neutrophils | C5a, MRSA | Neutrophil phagocytosis and killing ↑, respiratory burst, neutrophil transmigration ⇔ | NA | NA | NA | NA | Evans et al. [118] |
LZD | Mouse | BALF | H1N1 influenza virus, MRSA i.n. | TNF-α, IL-6 ↓ | ND | ↓ | ↓ | ↑ | Verma et al. [111] |
LZD | Rabbit | Lung tissue, whole blood | MRSA i.n. | TNF-α ↓ | ND | ND | ↓ | ND | Pauchard et al. [100] |
LZD | Mouse | BALF, lung tissue, alveolar macrophages | H1N1 influenza virus i.n., MRSA i.t. | KC/CXCL1, MIP-2, IFN-γ, TNF-α, IL-1β ↓ | ↓ | ↓ | ↓ | ND | Bhan et al. [110] |
LZD | Human (in vitro) | THP-1 monocytes | LPS | TLR-1, -2, -6 ↑, phagocytic activity ↓ | NA | NA | NA | NA | Bode et al. [114] |
LZD | Mouse | Lung tissue | MRSA t.t. | TNF-α, IL-1β, MIP-2 ↓ | ↓ | ↓ | ↓ | ND | Jacqueline et al. [97] |
LZD | Mouse | BALF, lung tissue | MRSA i.n. | IL-1β, IL-6, IL-17, IFN-γ ↓ | ND | ↓ | ↓ | ↑ | Chen et al. [99] |
LZD | Mouse | Lung tissue | H1N1 influenza virus, MRSA i.n. | IFN-γ, KC/CXCL1, IL-6 ↓, IL-1β, TNF-α, IL-12 ⇔ | ND | ND | ND | ND | Liu et al. [109] |
LZD | Mouse | BALF, lung tissue, TBLN | H1N1 influenza virus, S. pneumoniae i.n. | IFN-γ, TNF-α ↓ | ND | ND | ND | ND | Breslow-Deckman et al. [103] |
LZD | Human (ex vivo) | Whole blood | MRSA | IL-6, IL-8, MCP-1 ↓ | NA | NA | NA | NA | Franks et al. [113] |
LZD | Mouse | Lung tissue | MRSA i.n. | TNF-α, IL-6, IL-12 ↓ | ND | ND | ND | ND | Yoshizawa et al. [101] |
LZD | Mouse | BALF, lung tissue, alveolar macrophages | MRSA t.t. | MCP-5, IL-6, MMP-9 ↓, neutrophil apoptosis ↑, efferocytosis ⇔ | ↓ | ND | ↓ | ND | Akinnusi et al. [96] |
LZD | Piglet | BALF, lung tissue, serum, blood plasma | MRSA i.t. | TNF-α, IL-6 ⇔ | ND | ND | ↓ | ↑ | Luna et al. [98] |
LZD | Mouse | Lung tissue | MRSA i.v. | TNF-α, IL-1β, MIP-2 ↓ | ND | ND | ↓ | ↑ | Yanagihara et al. [148] |
LZD | Human (ex vivo) | PBMC | LPS | IL-1β, IL-6, TNF-α, IL-1RA ↓ | NA | NA | NA | NA | Garcia-Rocca et al. [112] |
LZD | Human (ex vivo) | PMN | MRSA, MSSA, VRE | Phagocytosis, production of superoxide, hydrogen peroxidase radicals ⇔ | NA | NA | NA | NA | Ballesta et al. [116] |
Fluoroquinolones | LVFX | Murine | BALF, lung tissue, blood | H1N1 influenza virus i.t. | IFN-γ, TNF-α ↓, oxidative and nitrative stress: NO metabolites, ROS ↓ | ND | ND | ↓ | ↑ | Enoki et al. [122] |
MOX | Human (ex vivo), mouse | BALF, lung tissue, blood plasma | S. pneumoniae i.n. | IL-6, IL-8, IL-1β, KC/CXCL1 ⇔ | ND | ↓ | ⇔ | ND | Müller-Redetzky et al. [126] |
MOX | Mouse | BALF, lung tissue, blood plasma | S. pneumoniae, P. aeruginosa i.n. | IL-1β, KC/CXCL1, IL-17A ↓, TNF-α expression in lung tissue ↓ | ↓ | ND | ↓ | ND | Beisswenger et al. [123] |
CPFX, LVFX, MOX | Mouse | BALF, serum | LPS i.t. | TNF-α, IL-1β, MIP-2 ↓ (CPFX) | ND | ↓ (CPFX), ⇔ LVFX, MOX | ↓ (CPFX), ⇔ LVFX, MOX | ↓ (CPFX), ⇔ LVFX, MOX | Huang et al. [124] |
MOX | Mouse | Lung tissue | C. albicans i.t., cyclophosphamide i.p. | TNF-α, KC/CXCL1 ↓, IL-2, IL-10, IFN-γ ⇔ | ND | ND | ↓ | ↑ | Shalit et al. [125] |
Epoxid antibiotic fosfomycin | FOM | Rat | Lung tissue | Caecal ligation and puncture | TLR-4, NF-κB, TNF-α, oxidative damage (TBARS ↓, -SH ↑) ↓ | ND | ND | ↑ | ND | Yildiz et al. [137] |
FOM | Human (ex vivo) | PMN | LPS | IL-6 ↓ | NA | NA | NA | NA | Ubugai et al. [149] |
FOM | Human (in vitro), mouse | THP-1 monocytes, alveolar epithelial cells (MLE-12), lung tissue, BALF | S. aureus i.v. | MAPK (JNK, ERK, p38), NLRP3 proteins and activation, IL-1β, IL-18, MPO ↓ | ↓ | ↓ | ↑ | ND | An et al. [138] |
FOM | Human (cohort study) | Whole blood | LPS | TNF-α, IL-1β, IL-6 ⇔ | NA | NA | NA | NA | Sauermann et al. [142] |
FOM | Human (ex vivo) | Whole blood | LPS | TNF-α, IL-1β, IL-6 ↓, IL-4, IL-10, IL-13 ⇔ | NA | NA | NA | NA | Zeitlinger et al. [140] |
FOM | Mouse | Serum | LPS | TNF-α, IL-1β ↓ | NA | NA | NA | NA | Matsumoto et al. [139] |
FOM | Human (ex vivo) | Monocytes | LPS | TNF-α, IL-1α, IL-1β, IL-1RA, GM-CSF↓ | NA | NA | NA | NA | Morikawa et al. [141] |
FOM | Human (ex vivo) | PMN | S. aureus | Phagocytosis and killing ↑ | NA | NA | NA | NA | Pérez Fernández et al. [136] |