In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

Abstract

Psoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1 alpha was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.

IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes

“…Its promotion of lymphocyte adherence in the present study may also have a bearing on the observation that blood lymphocytes from normal subjects bind to dermal endothelia exposed in tissue sections of psoriatic plaques, but not to those of uninvolved psoriatic skin or skin from normal subjects [36]. IL-6 is released from epidermal cells [8], keratinocytes [37] and fibroblasts [38], and the demonstration that IL-6 production by endothelial cells is stimulated by IL-1 [30] or IFN- [39] introduces the consideration that IL-6 could be having an autocrine feedback effect on endothelial cell function. An overproduction of IL-6 by fibroblasts from patients with progressive systemic sclerosis is thought to have a profound effect upon the course of this disease [40].…”

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines

“…Among the cytokines expressed in the skin are tumor necrosis factor-alpha (TNF-␣), interleukin (IL)-1, IL-6, chemotactic proteins, including macrophage inflammatory protein-2 (MIP-2), which allow for migration of polymorphonuclear leukocytes (PMNs) into the dermis, and cytokines that augment the activity of infiltrating cells, such as granulocytemacrophage colony-stimulating factor (GM-CSF) [6]. IL-6 expression by epidermal cells correlates with the formation of psoriatic lesions and may contribute to the pathogenesis by promoting growth of epidermal cells [7]. It has been suggested that sustained free radical production in tissues may have a role in cellular signaling by the mobilization of transcription factors, such as nuclear factor-B (NF-B) [8], which help regulate genes controlling inflammatory cytokines and chemokines [9][10][11].…”

Lack of Correlation between Interleukin 6 and Interleukin 1 Levels in Psoriatic Lesional Skin.

“…Based on the fact that the psoriatic lesions are not uniform but rather heterogeneous in regard to the position of highly inflamed portions, which are characterized by phase-wise transepidermal neutrophil chemotaxis, we speculate that IL-6 might be generated only in lesional skin under special circumstances like chemotactic C5a anaphylatoxin (Takematsu and Tagami 1993). In fact, Ohta et al (1991) demonstrated the strongest mRNA expression of both IL-6 and IL-6 receptors in the narrow transitional zone between perilesional uninvolved epidermis and fully developed psoriatic epidermis.…”

“…Therefore, we were intrigued to study whether the production of IL-6 correlates with the levels of IL-1 in psoriatic lesions. Most of the earlier studies on IL-6 in psoriasis have been performed immunohistochemically (Grossman et al 1989;Oxholm et al 1989;Ohta et al 1991). In the present study, we measured the levels of immunoreactive IL-6 in suction blister fluids as well as in the horny tissue extracts of psoriasis and related pustular dermatoses to evaluate the ongoing as well as the preceding events in the lesional skin and correlated their levels with those of immunoreactive IL-1.…”

“…It also stimulates the proliferation of human keratinocytes in culture (Grossman et al 1989; Krueger et al 1991) and this proliferative effects are suggested to be mediated indirectly via the epidermal growth factor/transforming growth factor-a receptor (Elder et al 1992). Thus IL-6 has been speculated to play an important role in the pathogenesis of psoriasis, and in fact its enhanced expression was demonstrated in the psoriatic lesional skin (Grossman et al 1989; Oxholm et al 1989; Prens et al 1990; Neuner et al 1991;Ohta et al 1991), together with the reports of its increased production by monocytes and of its elevated circulating levels (Grossman et al 1989; Neuner et al 1991).…”