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The role of ivermectin as an anti-inflammatory agent has only recently been understood. This is an integral part of its use as an antihelminthic agent. Ivermectin is now known to play an immunomodulatory role that suppresses inflammatory responses in humans [48]. It inhibits liposaccharide (LPS)-induced cytokine production [49]. Toll-like receptors on macrophages recognize LPS, which leads to sequential expression and secretion of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and integrin-β6 [48]. This is made possible by the ability of ivermectin to block the nuclear factor kappa-light-chain enhancer of the activated B (NF-κB) pathway that modulates the expression and production of proinflammatory cytokines [49]. This prevents toll-like receptor 4 from initiating a cascade that leads to the production of proinflammatory cytokines. It is suggested that this mode of action explains why ivermectin may be helpful in intensive care unit settings with increased risks of LPS-mediated bacterial infections [50]. Ali et al. demonstrated that increased levels of IL-17 in rosacea led to the production of proinflammatory cytokines such as IL-1 and TNFα through the nuclear factor kappa-light-chain enhancer of activated B (NF-κB) pathway, which is again inhibited by ivermectin [51]. This prevents NF-kB from allowing IL-17 to produce proinflammatory cytokines such as IL-1 and TNFα. In addition, ivermectin has been shown to inhibit signal transducer and activator of transcription 3 (STAT-3), which is responsible for upregulating proinflammatory markers in macrophages [50, 52]. The ability of ivermectin to modulate the production of proinflammatory cytokines plays a vital role in a wide range of pathological conditions.
