Distinct Serum Cytokine Levels in Drug– and Measles–Induced Exanthema

Abstract

Background: Macular or maculopapular skin reactions are frequent events in drug allergy as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship to drug intake or failure to detect virus–specific antibodies of the IgM class. Studies on drug–specific T cell lines and T cell clones isolated from drug–allergic patients have suggested that these cells may represent a significant source of IL–5. On the other hand, viral infections are frequently associated with elevated IFN–γ levels. Objective: Determination of serum–cytokine levels to differentiate between drug– and virally induced skin eruptions. Patients: 18 patients suffering from acute drug allergy and 19 patients with acute measles, rubella or parvovirus infection. Measurements: Cytokine–ELISA (IL–5, IL–4 and IFN–γ) of sera collected during acute drug allergy or during acute measles, rubella or parvovirus infection. Results: In 12/18 patients with drug allergy, IL–5 and/or IL–4 were elevated. A significant correlation (r_Spearman = 0.84) between IL–5 serum levels and eosinophil counts in the blood was found. No correlation was detected between IL–4 and blood eosinophilia or between IL–4 and IL–5 levels. After remission, IL–5 and IL–4 decreased to undetectable levels. IFN–γ on the other hand was not measurable in patients with drug allergy while elevated IFN–γ serum levels were detected in 17/19 patients with measles, rubella or parvovirus infection; 2 patients with acute virus infection had elevated IL–5, and/or IL–4 and IFN–γ levels. Conclusion: These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that the combined analysis of eosinophilia in the blood, IL–4 and IFN–γ might help in differentiating skin eruptions.

Guanylate-Binding Protein-1 Expression Is Selectively Induced by Inflammatory Cytokines and Is an Activation Marker of Endothelial Cells during Inflammatory Diseases

“…The latter finding is well in agreement with the locally restricted expression of ICs in these diseases. 22,[37][38][39][40][41][42][43][44] In summary, we show that GBP-1 expression is highly associated with endothelial cells in vivo and is selectively up-regulated by ICs in inflammatory skin diseases. These findings indicate that GBP-1 is a novel activation marker that characterizes the IC-activated phenotype of endothelial cells.…”

“…44,70 The tumorigenic interplay of these two viruses is mediated by the same ICs that have been shown to induce GBP-1 expression, and expression of all these cytokines has been demonstrated in KS tissue sections. 22,[37][38][39][40][41][42][43][44] In addition, in psoriasis and adverse drug reactions of the skin IFN-␥ expression has been detected. 39 -42 In contrast to healthy skin, GBP-1 was detected in each of the three different diseases of the skin with a high-inflammatory component.…”

“…22,[37][38][39][40][41][42][43][44] Notably, GBP-1 was detected in the inflammatory skin diseases and in KS ( Figure 5; B to E, left) but not in healthy skin ( Figure 5A, left, compare also Figure 3, E and F). In addition, in diseased skin, GBP-1 was selectively expressed in endothelial cells as indicated by simultaneous detection of GBP-1 and CD31 ( Figure 5; A to D; GBP-1: green, left; CD31: red, middle; co-localization: yellow, right, white arrows).…”

“…This is in agreement with the locally restricted expression of ICs that has been reported in all of these lesions. 22,[37][38][39][40][41][42][43][44] …”

Measles Virus Infection in Adults Induces Production of IL-10 and Is Associated with Increased CD4+CD25+ Regulatory T Cells

“…The primary cellular source of IL-10 in MV infection is not clear, although various cell types, including neutrophils and monocytes (19,23), have been suggested. Interestingly, IL-5 is either absent (24) or decreased during MV infection (19), probably reflecting varying levels of baseline IL-5 and eosinophilia. Cells infected with clinical strains of MV, but not vaccine strains, display nearly complete suppression of IFN-␣-induced antiviral state probably due to the activities of proteins encoded by the MV P gene (25).…”