**3.6 Host immune system modulators**

Also, some drugs that modulate host immune system have reported antibacterial activity against GNB. Tamoxifen, a SERM used for breast cancer treatment, can reduced the migration of immune cells from bone marrow to blood through the reduction of monocytes chemoattractant protein 1 (MCP-1) and IL-18 in a murine model of sepsis by *A. baumannii*, *P. aeruginosa* and *E. coli* [36]. Moreover, tamoxifen

has been shown to enhance the killing activity of macrophages and neutrophils against *A. baumannii* and *E. coli in vitro* [36]. Calcitriol, a bioactive form of vitamin D3 used to treat hypocalcemic conditions and renal osteodystrophy, has a similar mechanism of action which it has been described to enhance the killing activity of monocytes and macrophages towards *P. aeruginosa* [37]. Moreover, GTS-21, an anti-inflammatory drug, has presented therapeutic efficacy against *P. aeruginosa in vivo* by enhancing macrophage function via inhibiting the release of nuclear protein high mobility group box-1 (HMGB1) [39]. When GTS-21 is combined with M1 muscarinic acetylcholine receptor agonist and α7n-acetylcholine receptor agonist against *E. coli in vivo*, the blood concentrations of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were reduced significantly [38].
