**8.5. Antibiotic adjuvants potentiate anti-inflammatory properties of antibiotics**

There is limited information on the effectiveness of adjuvant therapy for the treatment of bacterial complications of influenza. In a very recent study [70], explored the adjuvant effect of polyactin (PA), an inactivated trivalent influenza virus (ITIV) with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Results showed that PA is a novel mucosal adjuvant for intranasal vaccination with the inactivated trivalent influenza vaccine that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

The inflammatory response of viral infections results in the excessive production of reactive oxygen species (ROS) in the cells and tissues, and antioxidant system cannot neutralize them. Imbalance in this protective mechanism can lead to the damage of cellular molecules such as DNA, proteins, and lipids [71]. Moreover, the role of ROS in inflammation has been investigated vigorously by earlier authors [72, 73]. ROS are thought to be key signaling molecules in the progression of inflammatory disorders. It induces inflammation by the induction of COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), and IL-6), chemokines (IL-8 and CXCR4), and pro-inflammatory transcription factors (NF-κB) [74]. Inflammatory cytokines trigger inflammation, causing the immune response to weaken which may help to increase the risk of bacterial infection. This rise in inflammatory markers with infection is a cascade reaction and is not easily broken only by antibiotics. Adjuvants have a major role to play here. Buret [75] reported that some antibiotics, such as the 16-membered macrolide tilmicosin, may generate anti-inflammatory benefits by modulating the production of pro-inflammatory mediators, and by inducing neutrophil apoptosis. Many studies have highlighted that adjuvants co-administered with antibiotics reduce the oxidative stress, which in turn reduce inflammation [76, 77]. Dwivedi et al. [78] reported that AAE used for 21 days, the levels of antioxidant enzymes (superoxidase dismutase, catalase, glutathione reductase, glutathione peroxidase), along with xanthine oxidase, lipid peroxidation, myeloperoxidase (MPO) levels, hepatic, and renal parameters were significantly improved in plasma and tissues of the AAEtreated group indicating antioxidant or free radical scavenging properties [50].

Osteomyelitis is an infection and inflammation in bone which is primarily caused by *S. aureus* and *S. epidermidis* and the levels of cytokines (TNFα and IL-6) is increased in osteomyelitis [79]. Dwivedi et al. [80] demonstrated that the combination of antibiotic along with adjuvant significantly improved the inflammatory cytokines (TNFα and IL-6), malondialdehyde (MDA), and myeloperoxidase in animal osteomyelitis infection model. From the earlier explanation, it may be concluded that compounds or drugs along with adjuvant generating both antibacterial and anti-inflammatory effects are likely to be most effective at treating bacteriainduced inflammatory syndromes.
