ANTI- INFLAMMATORY EFFECT OF AMITRAZ DUE TO INHIBITION OF THE GAMMA-INTERFERON PRODUCTION AND MITOCHONDRIAL ACTIVITY OF THE T LYMPHOCYTES.

Abstract

Amitraz, a formamidine pesticide, is one of the selected drugs for the treatment of the canine demodectic mange. Inflammatory alterations are found associated with the presence of high numbers of the mite Demodex canis in the skin. The reasons for the indication of amitraz are based only on its acaricide action. Some authors have suggested analgesic and anti-inflammatory properties for this drug, but few studies have been done to understand the mechanisms that prove such effect. To validate this suggested action, splenic cells from C3H/He mice were cultured and stimulated with either 5μg/mL of Concanavalin A (Con A) or 10μg/mL of lipopolysaccharide (LPS) from Escherichia coli 0111:B4 in the presence of 0.00; 0.78; 1.56; 3.13; 6.25 and 12.50μg/mL of amitraz diluted in arol or equivalent amount of solvent. The viability of the cells was significantly reduced when these cells were cultured for 48 hours with amounts equal or higher than 3.13 μg/mL of amitraz. The mitochondrial activity of spleen cells, analyzed by the MTT reduction method, did not change when amitraz was used in concentrations equal or higher than 1.56 μg/mL, although this activity was significantly reduced when the spleen cells were stimulated with Con A and then treated with amitraz. The proliferation of T lymphocytes stimulated with Con A did not change when amitraz was used in the concentrations equal or higher than 1.56μg/mL. The proliferation of B lymphocytes also did not change when spleen cells were treated with LPS. The production of IFN-γ was inhibited by amitraz in concentrations equal or higher than 1.56μg/mL. The results described here demonstrate that one of the possible mechanisms for the anti-inflammatory effect of amitraz relates to its ability of inhibiting the T lymphocyte metabolism and IFN-γ production, without affecting the proliferation of these cells. KEY -WORDS: Amitraz. T lymphocytes. IFN-γ. Arol. Canine Demodex.