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Inflammation of guinea pig dermis

Effects of leukotriene B4 receptor antagonist, SC-41930

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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-benzo-pyran-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 200μg 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.

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Authors and Affiliations

  1. Departments of Gastrointestinal Diseases, Research, and Pathology, Searle Research and Development, 4901 Searle Parkway, Skokie, Illinois

    D. J. Fretland, D. L. Widomski, J. M. Zemaitis, R. E. Walsh, S. Levin, S. W. Djuric, R. L. Shone, B. S. Tsai & T. S. Gaginella

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  1. D. J. Fretland
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Fretland, D.J., Widomski, D.L., Zemaitis, J.M. et al. Inflammation of guinea pig dermis. Inflammation 14, 727–739 (1990). https://doi.org/10.1007/BF00916375

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