Modulation of Cytokines Production by Indomethacin Acute Dose during the Evolution of Ehrlich Ascites Tumor in Mice

Abstract

The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNFα, IL-1α, IL-2, IL-4, IL-6, IL-10, and IL-13 and PGE2 level in peritoneal cavity. The results have shown that EAT induces PGE2 production and increases tumor cells number from the 10th day. The cytokine profile showed EAT induces production of IL-6 from 10th day and of IL-2 on 13th day; the other studied cytokines were not affected in a significant way. The indomethacin treatment of EAT-bearing mice inhibited the tumor growth and PGE2 synthesis from the 10th day. In addition, the treatment of EAT-bearing mice with indomethacin has stimulated the IL-13 production and has significantly inhibited IL-6 in the 13th day of tumor growth. Taken together, the results have demonstrated that EAT growth is modulated by PGE2 and the inhibition of the tumor growth could be partly related to suppression of IL-6 and induction of IL-13.

Piceatannol Affects Gastric Ulcers Induced by Indomethacin: Association of Antioxidant, Anti-Inflammatory, and Angiogenesis Mechanisms in Rats

“…Cumulatively the Indo group results indicate a severe gastric injury and delayed healing. One previous rat study showed that Indo induced the COX-2 expression [ 39 ]; simultaneously, another previous study revealed that Indo has been shown to induce the IL6/TNFα level and inhibited the PGE2 level [ 40 ]. While in normal gastric mucosa COX-1 is the predominant COX isoenzyme, there is increasing evidence that detectable amounts of COX-2 mRNA and protein are expressed both constitutively and inducible in gastric mucosa [ 41 ].…”

Drug repurposing and cytokine management in response to COVID-19: A review

“…The antiviral activity of indomethacin was shown to be associated with blocking viral replication [90] . However, another interesting pharmacological effect of indomethacin that could contribute to COVID-19 patient recovery is its capacity to modulate cytokine production [91] , [92] , particularly the robust effect this drug has on reducing the release of proinflammatory IL-6 [93] . The ability of indomethacin to attenuate inflammatory processes in combination with its antiviral properties make it a good candidate in the fight against the coronavirus.…”

Suppression of VEGF and inflammatory cytokines, modulation of Annexin A1 and organ functions by galloylquinic acids in breast cancer model

“…Tumor necrosis factor-alpha (TNF-α) is involved in tumor growth, angiogenesis and metastasis in EAC model 21 . In addition, interleukin (IL)-6 and prostaglandin E2 (PGE2) expressions were elevated in EAC and human ascetic tumors 22 , 23 . Inflammatory PGE2 expression is the result of overactivation of arachidonic acid pathway through the action of phospholipase A2 enzyme.…”