Clindamycin inhibits nociceptive response by reducing tumor necrosis factor-α and CXCL-1 production and activating opioidergic mechanisms

Abstract

Clindamycin, a bacteriostatic semisynthetic lincosamide, is useful in the management of infections caused by aerobic and anaerobic Gram-positive cocci, including bacteremic pneumonia, streptococcal toxic shock syndrome and sepsis. It has been recently demonstrated that clindamycin inhibits in vitro and in vivo inflammatory cytokine production. In the present study, we investigated the effects of clindamycin in acute and chronic models of pain and inflammation in mice and the underlying mechanisms. Intraperitoneal (i.p.) administration of clindamycin (400 mg/kg) increased the animal's latency to exhibit the nociceptive behavior induced by noxious heat (hot plate model). Intrathecal injection of clindamycin (2, 10 and 50 µg) also increased the animals' latency to exhibit the nociceptive behavior. Tactile hypersensitivity and paw edema induced by intraplantar (i.pl.) injection of carrageenan were attenuated by previous administration of clindamycin (200 and 400 mg/kg, i.p.). Clindamycin (100, 200 and 400 mg/kg, i.p.) also attenuated ongoing tactile hypersensitivity and paw edema induced by i.pl. injection of complete Freund's adjuvant (CFA). The antinociceptive activity of clindamycin (400 mg/kg, i.p.) in the hot plate model was attenuated by previous administration of naltrexone (5 and 10 mg/kg, i.p.), but not glibenclamide or AM251. CFA-induced production of TNF-α and CXCL-1 was reduced by clindamycin (400 mg/kg, i.p.). Concluding, clindamycin exhibits activities in acute and chronic models of pain and inflammation. These effects are associated with reduced production of TNF-α and CXCL-1 and activation of opioidergic mechanisms. Altogether, these results indicate that the clindamycin's immunomodulatory effects may contribute to a pharmacological potential beyond its antibiotic property.

Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades

“…Moreover, it can also lead to the movement of neutrophils, interfere with the function of gastric mucosal endothelial cells and cause gastric mucosal damage (44). TNF receptor can transmit survival and death signals to cells, which plays an important role in cell proliferation, differentiation, apoptosis, regulation of immune response, and induction of inflammation (45).…”

Comparative Efficacy of Different Oral Doses of Clindamycin in Preventing Post-Operative Sequelae of Lower Third Molar Surgery—A Randomized, Triple-Blind Study

“…Antibiotics aid the immune system in battling infection and subsequently dismiss the cause of inflammation and pain; however, some studies [ 30 , 31 ] state that such an action may be attributed to non-microbial activity. Although the antimicrobial effect of clindamycin is indisputable, some studies [ 32 , 33 ] have demonstrated that clindamycin may inhibit the production of tumor necrosis factor-alpha (TNFα), interleukin-1(IL-1), and cytokines. Therefore, its non-antimicrobial immunomodulatory influence should be emphasized.…”

Clindamycin as an Alternative Option in Optimizing Periodontal Therapy

“…Furthermore, clindamycin suppresses the release of proinflammatory cytokines, such as TNF-α and IL-1β, that cause further destruction to the periodontal tissues when released in excess by bacteria and neighboring cells. Thus, the reduced production of TNF-α and chemokine CXCL-1 is another mechanism mediating the clindamycin inhibitory effect on inflammatory conditions such as periodontitis [6].…”

“…It can also be administered intravenously and has a remarkable tissue distribution and increased efficiency for S. aureus infections [5]. Furthermore, clindamycin has been suggested to exert immunomodulatory properties due to the suppression of proinflammatory cytokine release and its effects on phagocyte function, which is considered superior to dexamethasone with regard to Porphyromonas gingivalis [6,7]. Finally, clindamycin induces morphological changes at the surface of bacteria to facilitate their destruction and stimulates chemotaxis, thus inducing the mobilization of polymorphonuclear leukocytes at the site of infection and bacteria phagocytosis [8].…”