Epidermal Interleukin-1 is Increased in Cutaneous T-Cell Lymphoma

Abstract

Interleukin-1 (IL-1) is a monocyte-derived polypeptide with immunoregulatory and proinflammatory functions. Although monocytes are the principle source of IL-1, other cells, such as keratinocytes, endothelial cells, renal mesangial cells, and neutrophils, produce a factor with IL-1 activity. The IL-1-like polypeptide produced by keratinocytes, epidermal-derived thymocyte-activating factor (ETAF), is similar on biological, biochemical, and molecular levels to monocyte-derived IL-1. Studies of IL-1 or ETAF have for the most part been undertaken using cell culture supernatants or cell lysates, and in situ localization of ETAF has not been demonstrated. Previous studies have suggested that ETAF is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL). To gain insights into the role of these cytokines in disease states, we investigated whether IL-1 could be localized in tissue sections using a direct immunofluorescence technique with a monoclonal antibody directed against IL-1. This monoclonal antibody partially inhibited ETAF activity and totally inhibited IL-1 activity in the co-stimulator assay and so could be used to detect IL-1 or ETAF. We studied skin biopsies from 10 healthy individuals, 10 patients with CTCL, and 11 patients with various inflammatory dermatoses. Intense epidermal fluorescence was demonstrated in all cases of CTCL, whereas minimal reactivity was visible in normal biopsies and the inflammatory dermatoses. Most patients with CTCL showed an intercellular pattern, while none of the normal controls or those with inflammatory dermatoses showed this pattern. An irrelevant IgM monoclonal antibody, used as a negative control, did not demonstrate epidermal staining. To further demonstrate specificity, we incubated the anti-IL-1 antibody with recombinant beta IL-1:Epidermal reactivity was completely blocked. In a separate experiment, COLO 16 cells, a squamous cell carcinoma cell line that constitutively produces ETAF, stained positively for the IL-1 antibody. We conclude that epidermal IL-1 is elevated in CTCL.