SPONTANEOUS RELEASE OF LEUKEMIA INHIBITORY FACTOR AND ONCOSTATIN-M ISINCREASED IN SUPERNATANTS OF SHORT-TERM ORGAN-CULTURES FROM LESIONAL PSORIATIC SKIN

Several cytokines are increased in psoriatic skin, mainly at the lesio nal level. Some of these mediators seem to be very important in the pa thogenesis of psoriasis since they are thought to stimulate keratinocy te proliferation and/or to drive the inflammatory changes associated w ith psoriasis. Among the proinflammatory modulators, hematopoietins, w hich are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. Th e hematopoietin family includes interleukin-6 (IL-6), interleukin-11 ( IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granuloc yte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CN TF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL- 11, have been found to be increased in psoriatic lesions, The present study adds new information concerning the spontaneous release of two h ematopoietins, namely LIF and OSM, in 48-h culture supernatants of les ional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using comm ercially availabe ELISA kits. The results are expressed as picograms p er milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05 - 13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, ran ge under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin ( median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0. 9 pg/mg, range 0.4 - 5.2 pg/mg) than in supernatants of nonlesional (m edian 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (medi an 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleuk in-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8 - 2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-1 76.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken to gether with the fact that at least two other hematopoietins (namely IL -6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietin s in inflammatory processes associated with psoriasis.