Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.

1 3‐hydroxy‐5‐trifluoromethyl‐N‐[2‐(2‐thienyl)‐2‐phenyl‐ethenyl]‐ benzo(B) thiophene‐2‐carboxamide (L‐652,343) is a 5‐lipoxygenase and cyclo‐oxygenase inhibitor in vitro. 2 In psoriasis increased concentrations of arachidonic acid transformation products are found in the lesional skin which may be important in the pathogenesis of the disease. We have measured the effect of orally administered L‐652,343 on the concentration of LTB4 and prostaglandins in the lesional skin. 3 Eight patients with stable chronic plaque psoriasis received 500 and 250 mg of L‐652,343, 12 h apart. A chamber technique was used to collect skin exudate samples from abraded plaques before and at 4, 24 and 48 h after the first dose. Exudates were analysed for LTB4 by a neutrophil chemokinesis assay and for PGE2 and PGD2 by RIA. 4 PGE2 and PGD2 levels were significantly reduced at 4 and 24 h after the first dose of L‐652,343 but LTB4 levels were not affected indicating inhibition of the cyclo‐oxygenase pathway but not of the 5‐lipoxygenase pathway. This shows the importance of confirming that the action of 5‐ lipoxygenase inhibiting drugs in vitro occurs in vivo.

Topical clobetasol propionate or vehicle ointment was applied daily for 3 days to psoriatic plaques on eight patients. Skin chamber exudates from untreated, steroid and vehicle treated lesions were assayed for arachidonic acid (AA), leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) before, and at 24 h and 72 h after treatment. Significant reductions in AA and LTB4 were observed at 72 h in steroid treated lesions. The reduction in 12-HETE levels observed after steroid treatment was not statistically significant. PGE2 levels in lesional psoriatic skin were unaltered. The reduction of AA, and LTB4 was associated with clinical improvement of psoriasis.

Collection of exudate from suction bullae is a commonly used method for sampling human skin for mediator analysis. It is satisfactory on skin of normal structure but is unreliable on lesional psoriatic skin in which there are major structural changes and excessive scaling. Collection of exudates from abraded sites was found to be a suitable alternative method for psoriatic skin. Arachidonic acid and 12-HETE, but not PGE2, were significantly higher in exudate from abraded lesional psoriatic skin (494 +/- 88, 45.9 +/- 4.2 and 9.6 +/- 1.8 ng/ml respectively, mean +/- sem, n = 5) compared to uninvolved skin (154 + 38, 18.5 + 5.1 and 7.7 + 1.9 ng/ml) or skin of normal volunteers (119 +/- 37, 14.5 +/- 6.7 and 4.5 +/- 1.6 ng/ml, n = 7) which were similar. The coefficient of variation for exudate collection and mediator analysis was usually less than 55%. The analysis of lipoxygenase and cyclooxygenase products was simplified by the use of chlorobutane to extract preferentially arachidonic acid and HETEs from neutral aqueous solutions.

Arachidonic acid and prostaglandins were measured in uninvolved psoriatic skin before and after treatment for up to 24 h with dithranol. Prior to treatment, skin exudate contained 2744 ng ml-1 arachidonic acid and 26.4 ng ml-1 PGE2. After treatment with dithranol, the arachidonic acid concentration increased to a maximum of 5556 ng ml-1 at 48 h whilst PGE2 increased to 93.4 ng ml-1 at 12 h and then declined. The erythemal response was apparent at 6-12 h and maximal at 72 h. These results suggest that PGE2 mediates the early development of dithranol erythema.

When polymorphonuclear leucocytes (PMN) elicited in mice were infected with Mycobacterium microti or Mycobacterium lepraemurium, phagosome-lysosome fusion occurred with both species. This contrasts with the situation in macrophages where phagosome-lysosome fusion is inhibited by M. microti but not M. lepraemurium. No evidence was found for killing of M. microti or M. lepraemurium when the bacteria were isolated from PMN and their viability tested in cell-free medium or macrophages.