Inflammation of guinea pig dermis. Effects of leukotriene B4 receptor antagonist, SC-41930

Inflammation. 1990 Dec;14(6):727-39. doi: 10.1007/BF00916375.

Abstract

Neutrophil (PMNL) infiltration is a prominent feature of human psoriasis. Psoriatic skin lesions contain abnormally high amounts of leukotriene B4 (LTB4), itself a potent PMNL chemoattractant both in vivo and in vitro. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-carboxylic acid), an orally active LTB4 receptor antagonist, was tested topically in models of skin inflammation induced by 200 nmol of the calcium ionophore A23187 or 200 micrograms phorbol-12-myristate-13-acetate (PMA) applied topically to the guinea pig ear as assessed by ear weight, levels of the PMNL marker enzyme myeloperoxidase (MPO), and histological examination (PMA model) at 4 and 18 h respectively. When coapplied topically with A23187 or PMA, SC-41930 significantly inhibited epidermal inflammation with ED50 values of 0.6 and 4 mg, respectively. SC-41930 treatment also was associated with lowered dermal LTB4 levels in both models. The PMA-induced skin inflammation model also was assessed histologically and revealed acanthosis, edema, PMNL infiltration, and rete ridge prominence as long as 96 h after a single application that was completely inhibited by SC-41930 topical coapplication. Furthermore, oral treatment (40 mg/kg) significantly reduced edema and inflammatory cell infiltration in both models. These models possess many of the characteristics of human psoriasis, and agents such as SC-41930 that demonstrate activity in these models may well have therapeutic utility in the treatment of human psoriasis.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Benzopyrans / pharmacology*
  • Calcimycin / toxicity
  • Disease Models, Animal
  • Guinea Pigs
  • Inflammation
  • Male
  • Psoriasis / pathology
  • Receptors, Immunologic / drug effects*
  • Receptors, Leukotriene B4
  • Skin / drug effects
  • Skin / pathology*
  • Tetradecanoylphorbol Acetate / toxicity

Substances

  • Benzopyrans
  • Receptors, Immunologic
  • Receptors, Leukotriene B4
  • SC 41930
  • Calcimycin
  • Tetradecanoylphorbol Acetate