Thiamine and riboflavin inhibit production of cytokines and increase the anti-inflammatory activity of a corticosteroid in a chronic model of inflammation induced by complete Freund's adjuvant

Pharmacol Rep. 2017 Oct;69(5):1036-1043. doi: 10.1016/j.pharep.2017.04.011. Epub 2017 Apr 23.

Abstract

Background: The effects induced by thiamine and riboflavin, isolated or in association with corticosteroids, in models of chronic inflammation are not known. Thus, we evaluated the effect induced by these B vitamins, isolated or in association with dexamethasone, on the mechanical allodynia, paw edema and cytokine production induced by complete Freund's adjuvant (CFA) in rats.

Methods: Chronic inflammation was induced by two injections of CFA. Nociceptive threshold, paw volume and body temperature were evaluated for 21days. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) contents were determined in paw tissue. Riboflavin (125, 250 or 500mg/kg) or thiamine (150, 300 or 600mg/kg) were administered per os (po), twice daily. Dexamethasone (0.5mg/kgday, po) was administered every three days.

Results: CFA induced long lasting mechanical allodynia and paw edema. Elevation of body temperature was observed for a short period. Riboflavin reduced neither paw edema nor mechanical allodynia. Thiamine did not change paw edema, but partially inhibited mechanical allodynia. Riboflavin (500mg/kg) and thiamine (600mg/kg) exacerbated the anti-inflammatory activity of dexamethasone. Riboflavin, thiamine and dexamethasone reduced TNF-α and IL-6 production. The association of dexamethasone with thiamine induced greater inhibition of IL-6 production when compared with that induced by dexamethasone.

Conclusions: Riboflavin and thiamine exacerbate the anti-inflammatory activity of dexamethasone and reduce production of TNF-α and IL-6.

Keywords: Corticosteroids; Cytokines; Inflammation; Riboflavin; Thiamine.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Freund's Adjuvant / therapeutic use*
  • Gene Expression Regulation / drug effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Riboflavin / administration & dosage
  • Riboflavin / pharmacology*
  • Thiamine / administration & dosage
  • Thiamine / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Dexamethasone
  • Freund's Adjuvant
  • Riboflavin
  • Thiamine