Role of prostanoids in the inflammatory reaction and their therapeutic potential in the skin

Abstract

Vasodilatory prostaglandins (PG), contributing to the inflammatory reaction, have gained considerable attention. It is becoming apparent that PG have pharmacological effects traceable to biological activities distinct from smooth muscle relaxation. The data from pharmacological experiments presented here indicate the diverse action of vasodilatory PG analogues in the skin of laboratory animals. Nocloprost, a stable PGE2 analogue, induced erythema in intact skin of rats when applied topically and inhibited in the same dose range an irritant-induced inflammatory reaction in the ears of mice. Iloprost, a stable PGI2 analogue, showed proinflammatory activity after local application by enhancing the leukotriene B4 induced cell infiltration in the skin of mice. The attenuation of the spreading of ear necrosis in mice, on the other hand, indicates an anti-ischemic therapeutic potential of iloprost. Research in the past has elucidated the influence of PG on the vascular component of inflammation, but the role of PG on the cellular component of inflammation is less clear. The diverse effects of PG in skin indicate the need for a better understanding of their local actions.

In Vivo Availability of Pro-Resolving Lipid Mediators in Oxazolone Induced Dermal Inflammation in the Mouse

“…We observed that MPO activity (used as an indirect measure of PMN infiltration) was significantly increased at 24 h after the challenge with OXA. This finding confirmed those made in various other models of dermal inflammation, in which the maximal neutrophilic infiltrate occurs at the same time point [ 38 – 40 ]. Although, in our model, the MPO activity at 48 h remained comparably high and did not decrease again until 72 h after the induction of the inflammation, the influence of 15-epi-LXA 4 on the PMN infiltration and likewise on the biosynthesis of pro- as well as anti-inflammatory and pro-resolving lipid mediators was examined after 24 h. We cannot compare the concentrations of prostaglandins, LTB 4 or various HETE with the inflammatory infiltrate, since these mediators were not analysed in previous publications dealing with dermal inflammation.…”

Lipoxin and Aspirin-Triggered 15-epi-Lipoxin Cellular Interactions Anti-Inflammatory Lipid Mediators

“…16-phenoxy-LXA 4 , which resists enzymatic degradation and is a potent inhibitor of neutrophil adhesion and transmigration in vitro (24), applied topically to mouse ear skin just prior to induction of inflammation, clearly blocks neutrophil infiltration in a concentration-dependent fashion. Thus the inhibitory actions of LX and 15-epi-LXA 4 stable analogs reviewed here provide additional evidence for the ability of LX and aspirin-triggered LX to block neutrophil migration, which appears to be a unique action of lipoxins when compared to other lipid mediators or eicosanoids that either initiate (i.e., LTB 4 ) or enhance (PGE 2 , PGI 2 ) this response in vivo (7,38). It is of particular interest to point out that other eicosanoid stable analogs such as the analog of PGI 2 , Iloprost, significantly enhance LTB 4 -induced leukocyte infiltration in this mouse ear model (38), as did PGE 2 (see Table 4).…”

Experimental approaches to lymphocyte migration in dermatology in vitro and in vivo

“…Yet another means of inducing leukocyte influx is the application of compounds with intrinsic pro‐inflammatory capacities (Table 2). Substances frequently used for this purpose comprise the stable prostaglandin analogue Iloprost (131) and the calcium ionophore A‐23187 (132). The former enhances leukotriene B 4 ‐induced inflammation, whereas the calcium ionophore‐induced inflammation is mediated by endogenous leukotriene B 4 .…”