(-)-Pimecrolimus

Pimecrolimus is a cell-selective inhibitor that primarily acts on T cells and mast cells. It exerts its pharmacological effects by inhibiting the secretion of pro-inflammatory cytokines (a class of cytokines that induce systemic inflammation) and is indicated for the treatment of various inflammatory skin diseases, such as plaque psoriasis, atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis [1].

In addition to inhibiting the secretion of pro-inflammatory cytokines in T cells and mast cells, pimecrolimus can also suppress the release of preformed inflammatory mediators in mast cells. Due to its strong target specificity, the possibility of impairing systemic immune responses when applied topically to the skin is extremely low [1]. Relevant experiments have confirmed that in peripheral blood leukocyte systems containing basophils or mast cells, pimecrolimus significantly inhibits anti-IgE-induced histamine release, with inhibition rates of 82% and 73% for basophils and mast cells, respectively; simultaneously, it can also inhibit the release of tryptase, leukotriene C4 (LTC4), and tumor necrosis factor α (TNF-α) [2].

In the dendritic cell (DC)-stimulated CD4⁺ T cell model, pimecrolimus can effectively inhibit the upregulation of CD25 and CD54 molecules and the surface expression of OX40. It also significantly suppresses T cell proliferation (half-maximal inhibitory concentration IC50 = 0.55 nM) and reduces the synthesis of interferon γ (IFN-γ) and TNF-α [3]. Animal experimental results show that pimecrolimus has a significant therapeutic effect on allergic contact dermatitis (ACD) in mice and rats; in the rat model of atopic dermatitis, it can effectively relieve pruritus symptoms and reduce skin inflammatory responses [1].

References:

[1].  Stuetz A, Grassberger M, Meingassner JG. Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. Semin Cutan Med Surg, 2001, 20(4): 233-241.

[2].  Zuberbier T, Chong SU, Grunow K, et al. The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils. J Allergy Clin Immunol, 2001, 108(2): 275-280.

[3].  Kalthoff FS, Chung J, Stuetz A. Pimecrolimus inhibits up-regulation of OX40 and synthesis of inflammatory cytokines upon secondary T cell activation by allogeneic dendritic cells. Clin Exp Immunol, 2002, 130(1): 85-92.