Evaluation of Anti-Inflammatory Activity of Metronidazole Treatment On Carrageenan Induced Paw Edema in Mice Original paper

What was studied?

The study investigated metronidazole’s in vivo anti-inflammatory effects using a well-established acute inflammation model. Researchers administered metronidazole orally at three doses (2, 20, and 200 mg/kg) to mice one hour before injecting carrageenan into the hind paws to induce localized inflammation. They measured paw thickness at multiple intervals up to 48 hours and quantified the levels of two key pro-inflammatory cytokines—IL-1β and TNF-α—via ELISA. Indomethacin, a nonsteroidal anti-inflammatory drug, served as the reference control.

Who was studied?

The study utilized Swiss albino male mice aged 8–12 weeks, maintained under standard laboratory conditions. Researchers divided the mice into five groups: a control group, an indomethacin-treated group, and three metronidazole groups receiving increasing doses. Each group contained eight mice for the paw edema assessments, and four mice per group were used for cytokine analysis. The study followed ethical guidelines for animal experimentation, with approval from the local ethics committee.

What were the most important findings?

Metronidazole demonstrated significant anti-inflammatory activity across all doses tested, reducing paw edema at 2, 4, 24, and 48 hours post-carrageenan injection. The study observed no dose-response relationship, indicating that even low doses achieved maximal therapeutic effect within the tested range. All metronidazole-treated groups exhibited a return to baseline paw thickness by 48 hours, unlike the control group, where inflammation persisted. When compared to indomethacin, metronidazole exhibited comparable potency in terms of edema inhibition at the 2-hour peak inflammatory window.

Crucially, metronidazole treatment significantly lowered IL-1β and TNF-α levels, two cytokines that mediate acute inflammation and immune cell recruitment. These results confirm that metronidazole’s anti-inflammatory effect is not solely attributable to its antimicrobial action, but also to its capacity to modulate cytokine production and vascular responses during acute inflammation.

The anti-inflammatory effects of metronidazole, observed independent of infection, suggest it may impact host-microbe immune dynamics. While the study did not evaluate microbial composition, the involvement of IL-1β and TNF-α implies that metronidazole may attenuate inflammation triggered by microbial byproducts or dysbiosis, a pattern also seen in conditions like rosacea, inflammatory bowel disease, and periodontitis, where microbiome-host interactions drive pathology. Understanding this host-modulating capability is essential in microbiome-sensitive prescribing, especially when balancing therapeutic efficacy with ecological impact.

What are the implications of this study?

This study confirms that metronidazole exerts robust anti-inflammatory effects in acute, non-infectious settings, challenging the assumption that its benefits derive only from antimicrobial activity. By downregulating key cytokines and resolving inflammation comparably to indomethacin, metronidazole shows promise as a dual-function therapeutic in conditions where inflammation persists without overt infection. Clinicians may consider these findings when prescribing metronidazole for dermatologic or gastrointestinal diseases with a suspected inflammatory component. Moreover, its cytokine-modulating effects suggest that metronidazole could influence microbiome-host immune feedback loops, a consideration critical to antibiotic stewardship and microbiome preservation.