Human Recombinant Interleukin-1α Is Proinflammatory in Normal Human Skin

Dowd, Pauline M.; Camp, R.D.R.; Greaves, Malcolm W.

doi:10.1159/000210749

Cited by 42 publications

(12 citation statements)

References 5 publications

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“…Injection of IL-1 into animal skin generally results in a neutrophil-rich inflammatory cell response (10,24), and it is therefore perhaps surprising that the predominant cell type in uninflamed skin of both lines of mice was of the macrophage/ monocyte lineage. However, these findings are consistent with data from injection of IL-1 (11) or TNF (25) into normal human skin, either of which may result in recruitment of many macrophage-like cells.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.

Groves

Mizutani

Kieffer

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

188

159

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Resting epidermal keratinocytes contain large amounts of interleukin 1 (IL-1), but the function of this cytokine in the skin remains unclear. To further define the role of IL-1 in cutaneous biology, we have generated two lines of transgenic mice (TgIL-1.1 and TgIL-1.2) which overexpress IL-la in basal keratinocytes. There was high-level tissuespecific expression of transgene mRNA and protein and large quantities of IL-lei were liberated into the circulation from epidermis in both lines. TgIL-1.1 mice, which had the highest level of transgene expression, developed a spontaneous skin disease characterized by hair loss, scaling, and focal inflammatory skin lesions. Histologically, nonlesional skin of these animals was characterized by hyperkeratosis and a dermal mononuclear cell infiltrate of macrophage/monocyte lineage.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, the proinflammatory effects of IL-1 injection into normal animals and human skin have been well documented (10)(11)(12).…”

mentioning

confidence: 99%

Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.

Groves

Mizutani

Kieffer

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

188

159

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“…Injection of recombinant IL-1 into dermis in both mouse and man leads to the generation of a local inflammatory infiltrate (25,26). Stratum corneum contains significant amounts of IL-1 (1 1,27) that, if introduced into the dermis, similarly induces brisk inflammation. More recently, proteins extracted from both heel callus (thickened stratum corneum) as well as viable cells from forearm epidermis were purified by distinct strategies, and chromatographic fractions were injected into the skin of volunteers (26).…”

Section: Interleukin 1 and Cutaneous Inflammationmentioning

confidence: 99%

Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations.

Kupper¹

1990

J. Clin. Invest.

276

152

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PerspectivesEpithelial tissues in general (and skin in particular) define boundaries between inside and outside, host and environment. Mammalian skin and its appendages are poised at the critical interface between the delicately balanced internal milieu ofthe host and the mercurial forces of the outside world. Human skin diseases characterized by histopathologically distinct patterns of infiltration by T cells, B cells, monocytes, and granulocytes (referred to collectively as leukocytes) number quite literally in the hundreds. To state that the pathophysiologic mechanisms involved in the evolution of such unique inflammatory infiltrates are poorly understood is to euphamize; yet, recent advances have begun to allow for the construction of hypothetical paradigms that address the issue of mechanism in cutaneous immune and inflammatory processes.While skin was once considered the inert canvas upon which immune and inflammatory processes were painted by the bone marrow-derived host defense system, it is becoming apparent that resident sessile cells of skin are perhaps no less important in the generation ofa cutaneous immune or inflammatory response. This contention is based upon two broad classes of observation. The first is that nonhematopoieticallyderived cells resident to skin (including dermal fibroblasts, endothelial cells, and epidermal keratinocytes and melanocytes) can produce various cytokines upon appropriate stimulation (reviewed in reference 1) that affect decisively the behavior and function of lymphocytes, granulocytes, and monocytes. The second class of observation is that several of these cytokines influence the expression of adhesion molecules on endothelial and epithelial cells (1, 2). Taken to their logical conclusions, these observations suggest that nonhematopoietically-derived cells of skin, by virtue of their potential for cytokine production, have the indirect capacity to trap appropriate classes of leukocytes within microvasculature at precise anatomical sites, guide them through vessel walls and through dermal tissue along chemotactic gradients, and then activate them in situ. This article will review some of the evidence for this special immunocompetence of the skin, especially with regard to newer observations relating to cytokine production. Cytokines in cutaneous tissuesIt is axiomatic that cells ofdistinct lineages must communicate during the successful localization and evolution of an inflammatory response, and cytokines comprise an important part of

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“…IL upon injection into human skin (6) and is released from the epidermal cells after ultraviolet (UV) radiation (7)(8)(9). Epidermal IL-I release not only recruits an inflammatory response, but also potentiates T cell subset activation and the nature of the subsequent inflammatory response (10).…”

Section: Introductionmentioning

confidence: 99%

“…IL-I has the ability to cause cutaneous inflammation (6), potentiate T cell activation ( 14), stimulate eicosanoid metabolism ( 15), induce fibroblast proliferation ( 16), upregulate endothelial cell adhesion molecule expression ( 17, 18), and potentially stimulate keratinocyte proliferation ( 19,20). Because each of these elements may be present in psoriatic skin (21)(22)(23)(24)(25)(26)(27)(28), overexpression of IL-I has been postulated as a possible trigger for this disease process.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 receptor antagonist in normal and psoriatic epidermis.

et al. 1992

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The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-lra) and ILla were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity ofthe IL-lra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-lra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-lra. The ratio of IL-lra to IL-la proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-lra was 20 kD, slightly larger than monocyte-derived IL-lra and equivalent to an intracellular variant of IL-lra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-lra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-lra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-lra and IL-la may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin. (J. Clin. Invest. 1992. 90:571-583.)

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Human Recombinant Interleukin-1α Is Proinflammatory in Normal Human Skin

Cited by 42 publications

References 5 publications

Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.

Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis.

Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations.

Interleukin-1 receptor antagonist in normal and psoriatic epidermis.

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