The action of tumor necrosis factor-alpha on rat mast cells

J Interferon Cytokine Res. 2000 Apr;20(4):377-82. doi: 10.1089/107999000312315.


Taking into account that cytokine tumor necrosis factor-alpha (TNF-alpha) and mast cells (MC) both are involved in inflammation, it seems of great importance to recognize their relationships. Therefore, we have studied whether recombinant human TNF-alpha (rHuTNF-alpha) can cause histamine secretion from rat peritoneal MC. We have also examined the effect of this cytokine on MC reactivity. We have established that TNF-alpha stimulates rat MC to histamine release in a concentration-dependent manner. TNF-alpha-induced histamine secretion was evoked by concentrations > 10-16 M and reached the maximum rate at a concentration of 10-10 M (histamine release 17.1% +/- 1.9%, mean +/- SEM). We have also noticed that pretreatment of MC with TNF-alpha (in a concentration of 10-16 M) significantly inhibited concanavalin A (ConA)-stimulated release of histamine, with the percent release decreasing to 51% of the control value. Treatment of mast cells with TNF-alpha resulted in a decrease of compound 48/80-dependent histamine release as well (the percent released histamine fell to 85% of the control value). This altered MC responsiveness was reversible. After 120 min of resting time, the MC reactivity came back to the initial values. We have concluded that TNF-alpha appears to be a direct stimulus for MC to release histamine, and it may regulate MC secretory function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Concanavalin A / pharmacology
  • Dose-Response Relationship, Immunologic
  • Female
  • Histamine Release / drug effects
  • Histamine Release / immunology
  • Humans
  • Kinetics
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism*
  • Peritoneal Cavity / cytology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Temperature
  • Tumor Necrosis Factor-alpha / pharmacology*
  • p-Methoxy-N-methylphenethylamine / pharmacology


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • p-Methoxy-N-methylphenethylamine