Dermal microdialysis in the dog: in vivo assessment of the effect of cyclosporin A on cutaneous histamine and prostaglandin D₂ release

Abstract

Dermal microdialysis, a relatively noninvasive technique, allows investigation of the changes in cellular mediators released during cutaneous allergic responses. This technique was used to evaluate the effect of cyclosporin A, an immunosuppressive drug used for treatment of canine atopic dermatitis, on the cutaneous release of two pro-inflammatory mediators following intradermal allergen challenge. Four beagle dogs spontaneously sensitized to Ascaris suum were treated for 1 month with oral cyclosporin A. At days 0, 15 and 30 of the treatment, dialysis probes were inserted into the skin of the back, and 20 microL of A. suum antigen was injected intradermally at each site. At timed intervals, dialysate was collected and assayed for histamine and prostaglandin D(2) and the wheal area was measured. Mean histamine concentration and wheal area were significantly lower at days 15 and 30 of treatment, compared with day 0. However, prostaglandin D(2) concentration was not significantly reduced. The inhibition in histamine release after intradermal challenge, by cyclosporin, confirms its anti-inflammatory action in the dog. Dermal microdialysis provides a useful tool for investigating canine allergic reactions and their modulation by drugs.

Microdialysis of Inflammatory Mediators in the Skin: A Review

“…Histamine release as well as prostaglandin synthesis have been investigated following mast cell activation in guinea pigs (29), rats (30,31), and dogs (18). following allergenic provocation in guinea pig skin, through the subcutaneous injection of compound 48/80 as well as the intravenous administration of ovalbumin (32), histamine levels increased significantly.…”

“…following allergenic provocation in guinea pig skin, through the subcutaneous injection of compound 48/80 as well as the intravenous administration of ovalbumin (32), histamine levels increased significantly. The effect of cyclosporin A on the allergen-induced release of histamine and prostaglandin D2 (PgD2) synthesis has been investigated in dogs (18). Whereas orally administered cyclosporine gradually reduced the allergen-induced histamine release and wheal formation over 30 days of treatment, the rate of PgD2 synthesis surprisingly remained unchanged.…”

“…Animal models of skin inflammation have certainly assisted in significant development, improvement and validation of the technique itself during the last decade. It is now widely acceptable that this method is a versatile, safe and valuable tool for skin inflammatory investigations in animals including a wide range of anti-inflammatory drugs for preclinical investigations in animal skin (18)(19)(20)(21).…”

Crosstalk the Microdialysis in Scientific Research: from Principle to its Applications

“…In Shinkai et al [96] another study had proven that the transdermal ketoprofen significantly reduced the PGE-2 skin content and the joint fluid. Brazis et al [97] studied the impact cyclosporin A on the Beagle dogs skin histamine and PGE-2 levels, the results showed that histamine levels were significantly decreased after treatment 15~30 days, but the PGE-2 levels did not change significantly, indicating that cyclosporine inhibiting the release of anti-inflammatory effects of histamine. Study the physiological mechanisms of skin diseases is also a major application areas DMD.…”

Determination of Histamine in Microdialysis Samples from Guinea Pig Skin by High-Performance Liquid Chromatography with Fluorescence Detection

“…Radioenzyme or spectrophotometric enzyme immunoassays [20][21][22][23] , high-performance liquid chromatography (HPLC) [24,25] and spectrofluorometric assays [26] have been used for analysis of histamine in animal and human skin microdialysis samples. However, these methods do not provide the sensitivity and selectivity required for the determination of trace levels of extracellular histamine, and/or they are too laborious or unsuitable for routine use in a standard analytical laboratory.…”