N.J. Fincham

1 Clinically normal human abdominal skin was irradiated with three minimal-erythema doses of ultraviolet B irradiation, (u.v.B). 2 Erythema was assessed visually, and exudate recovered by a suction bulla technique from normal skin, and at 10 min, 2, 6, 18, 24 and 48 h after irradiation. 3 Erythema was barely visible at 2 h, but increased to maximum at 24 h, which was maintained at 48 h. 4 Increased arachidonic acid and prostaglandin E2, F2 alpha and D2 concentrations in the exudate, measured by gas chromatography-mass spectrometry, accompanied the developing erythema, with the maximal rise of arachidonic acid, prostaglandin E2 and D2 occurring at the height of the erythema at 24 h. 5 At 48 h, still at the height of the erythemal response, arachidonic acid and PGE2 levels had returned to near normal. 6 Concentrations of arachidonic acid and of its products from the cyclo-oxygenase pathway, parallel the development of i.u.B. erythema in the first 24 h.

The presence of neutrophil chemoattractant material in aqueous extracts of lesional psoriatic scale has been investigated by use of an agarose microdroplet chemokinesis method in combination with ultrafiltration and high-performance liquid chromatography (HPLC). Fractions were also assayed for murine thymocyte co-stimulating activity. Aqueous extracts of psoriatic scale contained significantly greater neutrophil chemokinetic activity than extracts of scale from normal skin. Successive ultrafiltration of extracts showed that the chemokinetic material was 10 to 30 kd. Heat lability and gel filtration HPLC characteristics suggested that the major chemokinetically active material in aqueous extracts of psoriatic scale is different from C5a des arg. Reversed-phase HPLC of 0.1% trifluoroacetic acid/acetonitrile extracts of psoriatic scale revealed two clearly resolved peaks of chemokinetic activity, the major peak consistently containing thymocyte co-stimulating activity. No significant neutrophil chemokinetic activity was seen in fractions after reversed-phase HPLC of scale from normal skin. These findings suggest that a major portion of the neutrophil chemoattractant activity in aqueous extracts of psoriatic scale is due to interleukin 1-like material, which may play a role in the pathogenesis of this disease.

The IL-1-like neutrophil chemoattractant activity previously reported by us to be present in the stratum corneum of psoriatic skin lesions has now been characterized further. Aqueous extracts of stratum corneum samples from psoriatic lesions and from the heels of normal volunteers were ultrafiltered to yield 10- to 30-kDa fractions. The ultrafiltered psoriatic preparations consistently contained greater neutrophil chemokinetic activity than the normal heel preparations, but in contrast the latter contained markedly greater IL-1 activity than the former. Successive chromatographic purification of psoriatic lesional stratum corneum extracts showed that the neutrophil chemokinetic material previously reported to co-elute with IL-1 activity on reversed phase HPLC, but to be distinct from C5a des arg, could now be separated by anion exchange HPLC into at least four different chemokinetic compounds that were also resolved from the IL-1 activity. The reversed phase HPLC-purified chemokinetic material from psoriatic stratum corneum was also active in a neutrophil chemotaxis assay. These findings show that samples from psoriatic skin lesions contain a group of novel 10- to 30-kDa neutrophil chemoattractant compounds that are distinct from both C5a des arg and IL-1. The contrasting neutrophil chemokinetic and IL-1 activities in psoriatic lesional and normal heel stratum corneum preparations support the finding that the two activities are produced by different compounds. These neutrophil chemoattractant and IL-1-like compounds may be of pathogenic importance in inflammatory skin disease.